A gel adhesive patch and its preparation method and application

Abstract

The invention discloses a gel adhesive patch, the components of which are an amide compound of N-cyclohexyl-N-cyclohexylcarbamoyl, acrylic acid N-hydroxysuccinimide fat, acrylic acid and a photoinitiator, and the preparation method thereof is to dissolve the amide compound of N-cyclohexyl-N-cyclohexylcarbamoyl, acrylic acid N-hydroxysuccinimide fat, acrylic acid and a photoinitiator in ultrapure water to obtain a uniform precursor solution; the precursor solution is injected into a mold and cured by light; after curing, a gel adhesive patch is obtained. The gel adhesive patch of the present invention has excellent mechanical properties, anti-swelling properties and bonding strength, can be applied to skin and internal organs, and has good application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of medical patches, and in particular to a gel adhesive patch and a preparation method and application thereof. Background Art

[0002] When the skin is damaged or has a large area of ​​trauma, burns or infected trauma, gauze and other dressings are often used to isolate bacteria, which slows down the healing process of the skin. If the treatment is not timely, it may lead to more serious consequences. In recent years, hydrogels have gradually become a research hotspot due to their low price, skin-friendly, moisturizing and good biocompatibility, and have been applied in many fields.

[0003] For example, Chinese patent document CN116392629A, published on July 7, 2023, discloses a multifunctional hydrogel dressing and its preparation method and application, which has good mechanical properties, excellent biological tissue adhesion, broad-spectrum antibacterial and antioxidant properties. Another example is patent document CN115350321A, published on November 18, 2022, which discloses a hydrogel dressing and its preparation method, which has excellent film-forming and moisturizing properties and has a significant ability to promote wound healing rate. However, the above-mentioned hydrogel dressing is mainly used for skin wounds and cannot be used in wet environments such as internal organs.

[0004] Although there are many hydrogel adhesive materials with different excellent properties, it is still necessary to develop a gel adhesive product with comprehensive properties and simple preparation method. Summary of the invention

[0005] In view of the problem that existing hydrogel adhesive materials cannot be used in wet environments, the purpose of the present invention is to provide a gel adhesive patch and its preparation method and application, which has excellent mechanical, anti-swelling and strong adhesive effects and can be used for adhesion in wet environments such as skin or internal organs.

[0006] In the first aspect, the present invention provides a gel adhesive patch, which contains an N-cyclohexyl-N-cyclohexylcarbamoyl amide compound, acrylic acid N-hydroxysuccinimide, acrylic acid and a photoinitiator. The formula of the gel adhesive patch is as follows by mass percentage: the content of N-cyclohexyl-N-cyclohexylcarbamoyl amide compound is 1-12%; the content of acrylic acid is 30-70%; the content of acrylic acid N-hydroxysuccinimide is 1-10%; the content of photoinitiator is 0.1-1%; and the balance is ultrapure water.

[0007] More preferably, the gel adhesive patch contains, by mass percentage: 1-4% of N-cyclohexyl-N-cyclohexylcarbamoyl amide compound; 56% of acrylic acid; 4% of acrylic acid N-hydroxysuccinimide; 0.1% of photoinitiator; and the balance is ultrapure water.

[0008] More preferably, the photoinitiator is selected from any one or a combination of phenyl-2,4,6-trimethylbenzoyl lithium phosphite (CAS No.: 85073-19-4), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (CAS No.: 106797-53-9), phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (CAS No.: 162881-26-7), 1-hydroxycyclohexyl phenyl ketone (CAS No.: 947-19-3), and 2,2-dimethoxy-phenylacetophenone (CAS No.: 24650-42-8).

[0009] More preferably, the photoinitiator is phenyl-2,4,6-trimethylbenzoyl lithium phosphite.

[0010] More preferably, the N-cyclohexyl-N-cyclohexylcarbamoyl amide compound has a structure shown in Formula II:

[0011] ,

[0012] Formula II.

[0013] In a second aspect, the present invention provides a method for preparing the above-mentioned gel adhesive patch, which specifically comprises the following steps:

[0014] N-cyclohexyl-N-cyclohexylcarbamoyl amide compound, acrylic acid N-hydroxysuccinimide ester, acrylic acid, and photoinitiator are dissolved in ultrapure water to obtain a uniform precursor solution; the precursor solution is injected into a mold and cured by light; after curing, a gel adhesive patch is obtained.

[0015] As a preferred example, during curing, the wavelength of light is 300 to 700 nm, and the irradiation time is 2 to 60 min.

[0016] More preferably, during curing, the wavelength of light is 365 nm and the irradiation time is 10 min.

[0017] In a third aspect, the present invention provides the use of the above-mentioned amide compound or gel adhesive patch in the preparation of skin and viscera adhesive products.

[0018] Beneficial effects of the present invention:

[0019] The invention provides a new amide compound for preparing a gel material. A gel adhesive patch containing the amide compound has excellent anti-swelling performance, with a minimum swelling rate of 128.3% after 24 hours, and then tends to be stable; the tensile strength before swelling equilibrium can reach 14.68MPa, and the mechanical properties are excellent; at the same time, the bonding strength is high, and the bonding strength on the surface of pig skin can reach 105.1kPa, and the bonding strength on the surface of pig liver can reach 57.2kPa. It also has better adhesion on the skin and internal organs, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The H1NMR spectrum of the amide compound of N-cyclohexyl-N-cyclohexylcarbamoyl.

[0021] Figure 2 LC-MS spectrum of N-cyclohexyl-N-cyclohexylcarbamoyl amide compound. DETAILED DESCRIPTION

[0022] The technical content of the present invention is further described below in conjunction with the examples: The following examples are illustrative, not restrictive, and the protection scope of the present invention cannot be limited by the following examples. The test methods used in the following examples are usually based on conventional conditions or conditions recommended by the manufacturer unless otherwise specified. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial sources.

[0023] Example 1 Preparation of N-cyclohexyl-N-cyclohexylcarbamoylamide compounds

[0024] 122.4 g of dicyclohexylcarbodiimide (DCC) and 12.32 g of 4-dimethylaminopyridine (DMAP) were added to 122 mL of dichloromethane (DCM), and 35.75 g of acrylic acid was slowly added under ice bath conditions, and the reaction was carried out at room temperature for 12 h. The reaction solution was filtered to remove impurities, and the crude product was obtained by vacuum drying. The crude product was separated and purified by TLC method using methanol: dichloromethane volume ratio of 1:7 as the developing solvent, and column chromatography was used to separate and purify the crude product using methanol and dichloromethane volume ratio of 1:10 as the eluent, and concentrated and dried to obtain a white solid with a yield of 76%. The obtained N-cyclohexyl-N-cyclohexylcarbamoyl amide compound is N-cyclohexyl-N-(cyclohexylcarbamoyl)acrylamide, and the structural formula is shown below:

[0025] ,

[0026] Its H 1 NMR spectrum Figure 1 As shown, H 1NMR(400MHz, DMSO): δ8.35(m,1H), δ6.32(m,1H), δ6.16(m,1H), δ5.69(dd,1H), δ4.01(m,1H), δ3.47(m,1H), δ1.73(m,8H), δ1.47(m,4H), δ1.14(m,8H). The LC-MS spectrum is as follows Figure 2 As shown, MS (EI): m / z 279 (M+H + ).

[0027] Example 2 Preparation of gel adhesive patch

[0028] The N-cyclohexyl-N-(cyclohexylcarbamoyl)acrylamide, acrylic acid N-hydroxysuccinimide, acrylic acid, phenyl-2,4,6-trimethylbenzoyl lithium phosphite and ultrapure water prepared in Example 1 were mixed in the ratio shown in Table 1 to prepare a uniform precursor solution, which was then injected into a mold and cured by light. The percentages in Table 1 are weight percentages. The wavelength of the light was 365 nm, the illumination time was 10 min, and the gel adhesive patch was obtained after curing.

[0029] Table 1 Comparison table of preparation ratios of various gel adhesive patches

[0030]

[0031] Example 3 Performance test of gel adhesive patch

[0032] 1. Test of swelling properties

[0033] Weigh 0.1 g of the gel adhesive patch prepared in Example 2 and record it as the initial weight (W0), and place it in 15 mL of normal saline. Take out the swollen hydrogel from the normal saline at a fixed time period, gently wipe off the excess water on the surface and record the mass of the gel, which is recorded as W t , and then the hydrogel was placed back into saline.

[0034] The swelling ratio (SR) of the hydrogel can be calculated by the formula: SR = (W t-W0) / W0×100%. A gel patch of fixed mass was placed in a physiological saline solution, and the mass of the gel was observed and recorded for a fixed time period. The results are shown in Table 2. With the addition of N-cyclohexyl-N-(cyclohexylcarbamoyl)acrylamide, the swelling rate decreased, and its swelling rate was inversely proportional to the amount of N-cyclohexyl-N-(cyclohexylcarbamoyl)acrylamide added, and reached a stable state after 24 hours. This may be because the addition of new compounds increases the cross-linking density of the cross-linked gel network, thereby inhibiting further swelling of the gel, while the low swelling hydrogel can maintain its original shape and mechanical properties. When high swelling is not required in narrow parts of the organism or biological adhesion, low swelling gel products need to be selected.

[0035] Table 2 Comparison of swelling properties of various gel adhesive patches

[0036]

[0037] 2. Tensile performance test

[0038] The tensile properties of the hydrogel strips before and after swelling equilibrium were tested using an intelligent electronic tensile testing machine, and the tensile speed was set to a constant 100mm / min. Before the test, the hydrogel strips were cut into dumbbell shapes. The gauge length of the dumbbell-shaped gel patch was 12mm, the width was 2mm, and the thickness was 0.5mm. The tensile strength of the gel patch is determined by the ratio of the maximum force to the cross-sectional area. Each group was repeated 3 times to reduce the error. The results are shown in Table 3. After adding N-cyclohexyl-N-(cyclohexylcarbamoyl)acrylamide, the tensile strength of groups 2-6 before and after swelling equilibrium increased, indicating that the addition of the new compound can enhance the tensile strength of the gel patch.

[0039] Table 3 Comparison of tensile strength of various gel adhesive patches

[0040]

[0041] 3. Adhesion performance test

[0042] The adhesion strength between the gel adhesive patch and the moist tissue (pig skin or liver) was tested by tensile shear performance test using a tensile testing machine to evaluate the adhesion performance of the gel adhesive patch. All moist tissues (pig skin or liver) were 7 cm in length and 2.5 cm in width; poly(methyl methacrylate) film was used as the hard backing tissue with Krazy glue, which was 10 cm in length and 2.5 cm in width; the gel patch adhesion area was 2.5 cm × 1 cm. Before adhesion to the pig skin or liver, the pig skin was infiltrated with PBS to simulate the moist physiological environment in vivo. Specifically, the gel adhesive patch was sandwiched between moist tissues and tested after initial pressure application for 24 h to ensure the balanced expansion of the adhered gel adhesive patch in a moist environment. During the adhesion process, the adhered part was covered with a ziplock bag to prevent the tissue and adhesive film from drying. The gel adhesive patch was tested using a tensile testing machine at room temperature, with a constant tensile rate of 50 mm / min set until the adhesion area was separated from the gel adhesive patch. The tensile shear strength of the gel adhesive patch was determined by dividing the maximum force by the initial adhesion area. Each group was repeated 3 times and the results were averaged. The results are shown in Table 4. The adhesion strength on the pig skin and pig liver surfaces of Group 1 was the highest. After adding N-cyclohexyl-N-(cyclohexylcarbamoyl)acrylamide, the adhesion strength decreased to some extent, but the adhesion strength on the pig skin and pig liver surfaces of Groups 2 and 3 was still relatively high, better than Groups 4-6, indicating that they can also have higher adhesion strength in a wet environment.

[0043] Table 4 Comparison of adhesion strength of various gel adhesive patches

[0044]

[0045] The preferred specific embodiments of the present invention are described in detail above. It should be understood that ordinary technicians in the field can make many modifications and changes based on the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by technicians in the technical field based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the scope of protection determined by the claims.

Claims

1. A gel adhesive patch, characterized in that: The gel adhesive patch contains an N-cyclohexyl-N-cyclohexylcarbamoyl amide compound, acrylic acid N-hydroxysuccinimide, acrylic acid and a photoinitiator. The formula of the gel adhesive patch is as follows by mass percentage: the content of the N-cyclohexyl-N-cyclohexylcarbamoyl amide compound is 1-12%; the content of acrylic acid is 30-70%; the content of acrylic acid N-hydroxysuccinimide is 1-10%; the content of the photoinitiator is 0.1-1%; the balance is ultrapure water; the N-cyclohexyl-N-cyclohexylcarbamoyl amide compound has a structure shown in Formula II: , Formula II.

2. The gel adhesive patch according to claim 1, characterized in that The gel adhesive patch contains the following mass percentages: 1-4% of N-cyclohexyl-N-cyclohexylcarbamoyl amide compound; 56% of acrylic acid; 4% of acrylic acid N-hydroxysuccinimide; 0.1% of photoinitiator; and the balance is ultrapure water.

3. The gel adhesive patch according to claim 1 or 2, characterized in that: The photoinitiator is phenyl-2,4,6-trimethylbenzoyl lithium phosphite.

4. A method for preparing the gel adhesive patch according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: dissolving an amide compound of N-cyclohexyl-N-cyclohexylcarbamoyl, acrylic acid N-hydroxysuccinimide, acrylic acid and a photoinitiator into ultrapure water to obtain a uniform precursor solution; injecting the precursor solution into a mold and curing it by light; and obtaining a gel adhesive patch after curing.

5. The preparation method according to claim 4, characterized in that: During the curing, the wavelength of the light is 300 to 700 nm, and the illumination time is 2 to 60 minutes.

6. Use of the gel adhesive patch according to any one of claims 1 to 3 or the gel adhesive patch prepared by the preparation method according to claim 4 in the preparation of skin and visceral adhesive products.

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