Medical pressure-sensitive adhesive as well as preparation method and application thereof

Abstract

The invention discloses a medical pressure-sensitive adhesive as well as a preparation method and application thereof, and belongs to the field of medicinal materials. The preparation method of the medical pressure-sensitive adhesive comprises the following steps: (1) uniformly mixing acrylic acid, glycerol, epigallocatechin gallate and a photoinitiator according to a weight ratio to prepare a precursor solution; and (2) pouring the precursor solution into a polytetrafluoroethylene mold, and curing by ultraviolet irradiation to obtain the medical pressure-sensitive adhesive. The medical pressure-sensitive adhesive provided by the invention has excellent dry / wet adhesion performance, good biocompatibility and efficient antibacterial performance.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of adhesive materials, and particularly relates to a medical pressure-sensitive adhesive as well as a preparation method and application thereof. BACKGROUND

[0002] Pressure-sensitive adhesive is a kind of high polymer material that can quickly adhere to the contact surface under slight pressure and can maintain the adhesion strength for a long time. Due to its biocompatibility, safety and convenience, it is widely used in the medical field and becomes a key component of modern medical consumables and instruments.

[0003] CN115181208A discloses a medical pressure-sensitive adhesive with iodine slow-release effect, a pressure-sensitive adhesive tape and a preparation method thereof. The patent forms a solvent type pressure-sensitive adhesive by copolymerizing N-vinyl pyrrolidone, polyethylene glycol diacrylate and acrylic ester monomer, and loads iodine in a complex way. After the adhesive tape is attached to the skin, iodine can be slowly released to achieve long-acting antibiosis, which is suitable for wound dressing, surgical film and other scenes. The advantages are high iodine loading amount and significant slow-release effect, but the improvement of adhesion strength or the recyclability design is not mentioned.

[0004] CN108795329A discloses a medical pressure-sensitive adhesive and a preparation method thereof. The pressure-sensitive adhesive takes natural rubber (70-90 parts) and gum rosin (30-50 parts) as core raw materials, adds components such as silicone rubber and acetylene carbon black, and is prepared by vulcanization process. The characteristics are that it has the properties of high temperature resistance, acid and alkali resistance and low temperature resistance, but the biological compatibility test data in the formula is not clear, which may have the risk of irritating sensitive skin.

[0005] CN119979075A discloses a high-performance acrylic pressure-sensitive adhesive and a preparation method thereof. The pressure-sensitive adhesive is copolymerized by acrylic monomers (80-100 parts), epoxy resin (2-8 parts) and functional monomers, and the epoxy group is used to enhance the adhesive property, which has the advantages of high temperature resistance, high humidity resistance and weather resistance. The glue does not need additional crosslinking agent, which simplifies the production process, but does not involve the design of drug controlled release or antibacterial function.

[0006] In summary, the existing medical pressure-sensitive adhesive material itself does not have therapeutic function, and usually needs to add bioactive substances (such as nano-silver, zinc oxide, graphene and antibacterial peptides) to accelerate wound tissue healing. Although these active substances have significant advantages in low drug resistance induction and potential drug film, they have potential cytotoxicity, insufficient stability, influence on the mechanical properties and adhesion properties of pressure-sensitive adhesive, and poor targeting, which limits their wide application in medical pressure-sensitive adhesive. SUMMARY

[0007] In view of the deficiencies of the prior art, the present application aims to provide a medical pressure-sensitive adhesive and a preparation method and application thereof, which has excellent dry / wet adhesion strength, good biocompatibility and high antibacterial performance, and can be used for the treatment of acute wound care.

[0008] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0009] In a first aspect, the present application provides a medical pressure-sensitive adhesive, wherein the preparation raw materials of the medical pressure-sensitive adhesive comprise acrylic acid, glycerol, epigallocatechin gallate and a photoinitiator.

[0010] In the present application, the medical pressure-sensitive adhesive is prepared by inducing the polymerization of acrylic acid to form polyacrylic acid under the action of ultraviolet light, and then cross-linking with glycerol and epigallocatechin gallate through hydrogen bonding. The polyacrylic acid and glycerol have hydrophilicity, can absorb water molecules on the surface of the wound tissue, and then adhere to the wound tightly by using the adhesion of epigallocatechin gallate. In addition, glycerol and epigallocatechin gallate have excellent antibacterial and anti-inflammatory effects, and the synergistic effect of the two active substances can accelerate the healing of tissue wounds.

[0011] Preferably, the present application provides a medical pressure-sensitive adhesive, wherein the preparation raw materials of the medical pressure-sensitive adhesive are in a proportion (total amount is 100 parts) of: 10-78 parts of acrylic acid, 20-88 parts of glycerol, 0-15 parts of epigallocatechin gallate and 0.01-0.1 parts of a photoinitiator.

[0012] Further preferably: 50-60 parts of acrylic acid, 30-38 parts of glycerol, 4-14 parts of epigallocatechin gallate and 0.04-0.06 parts of a photoinitiator;

[0013] More preferably: 55.50 parts of acrylic acid, 35.46 parts of glycerol, 8.99 parts of epigallocatechin gallate and 0.05 parts of 2,2-dimethoxy-2-phenylacetophenone.

[0014] In a second aspect, the present application provides a preparation method of the medical pressure-sensitive adhesive according to the first aspect, wherein the preparation method of the medical pressure-sensitive adhesive is as follows:

[0015] (1) uniformly mixing acrylic acid, glycerol, epigallocatechin gallate and a photoinitiator according to a weight ratio to prepare a precursor solution;

[0016] (2) pouring the precursor solution into a polytetrafluoroethylene mold, and irradiating and curing under ultraviolet light to obtain the medical pressure-sensitive adhesive.

[0017] Preferably, the photoinitiator comprises any one of 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenylpropanone, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide or a combination of at least two of benzophenone and 2,2-dimethoxy-2-phenylacetophenone.

[0018] Preferably, the wavelength of the ultraviolet light in the ultraviolet light irradiation curing is 254-405nm (e.g. 260nm, 280nm, 300nm, 320nm, 340nm, 360nm, 380nm or 400nm, etc.), and the energy is 100-1000W / cm 2 (e.g. 200W / cm 2 , 300W / cm 2 , 400W / cm 2 , 500W / cm 2 , 600W / cm 2 , 700W / cm 2 , 800W / cm 2 or 900W / cm 2 , etc.).

[0019] Preferably, the time of the ultraviolet light irradiation curing is 5-10min (e.g. 5.5min, 6min, 6.5min, 7min, 7.5min, 8min, 8.5min, 9min or 9.5min, etc.).

[0020] In a third aspect, the present application provides a use of the medical pressure-sensitive adhesive as described in the first aspect in wound dressing, surgical film, indwelling needle fixation and stoma infection prevention. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 The medical pressure-sensitive adhesive provided for Example 6 is used to show the adhesion effect on different substrates.

[0022] Figure 2 The medical pressure-sensitive adhesive provided for Example 3 and Example 6 is used to show the comparison of wet adhesion performance. DETAILED DESCRIPTION

[0023] The technical solutions of the present application are further illustrated by the specific embodiments. Those skilled in the art should understand that the embodiments are only used to help understand the present application and should not be regarded as specific limitations of the present application.

[0024] Some components in the examples are as follows:

[0025] Acrylic acid (AA): CAS No. 79-10-7, purchased from Shanghai Aldrich Biochemical Technology Co., Ltd.

[0026] Glycerol (GLY): Glycerin, CAS No. 56-81-5, purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0027] Epigallocatechin gallate (EGCG): CAS No. 989-51-5, purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0028] 2,2-Dimethoxy-2-phenylacetophenone (DMAP): CAS No. 24650-42-8, purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0029] Example 1

[0030] The present example provides a medical pressure sensitive adhesive and a preparation method thereof, and the preparation method of the medical pressure sensitive adhesive is as follows:

[0031] (1) uniformly mixing 28.12 parts of acrylic acid, 71.86 parts of glycerol and 0.02 parts of 2,2-dimethoxy-2-phenylacetophenone to prepare a precursor solution;

[0032] (2) pouring the precursor solution into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide, and 2 mm high), and irradiating with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure sensitive adhesive.

[0033] Example 2

[0034] The present example provides a medical pressure sensitive adhesive and a preparation method thereof, and the preparation method of the medical pressure sensitive adhesive is as follows:

[0035] (1) uniformly mixing 43.88 parts of acrylic acid, 56.07 parts of glycerol and 0.05 parts of 2,2-dimethoxy-2-phenylacetophenone to prepare a precursor solution;

[0036] (2) pouring the precursor solution into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide, and 2 mm high), and irradiating with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure sensitive adhesive.

[0037] Example 3

[0038] The present example provides a medical pressure sensitive adhesive and a preparation method thereof, and the preparation method of the medical pressure sensitive adhesive is as follows:

[0039] (1) uniformly mixing 60.98 parts of acrylic acid, 38.96 parts of glycerol and 0.06 parts of 2,2-dimethoxy-2-phenylacetophenone to prepare a precursor solution;

[0040] (2) Pour the precursor solution into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide, and 2 mm high), and irradiate with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure-sensitive adhesive.

[0041] Example 4

[0042] The present embodiment provides a medical pressure-sensitive adhesive and a preparation method thereof, and the preparation method of the medical pressure-sensitive adhesive is as follows:

[0043] (1) Mix 70.08 parts of acrylic acid, 29.85 parts of glycerol, and 0.07 parts of 2,2-dimethoxy-2-phenylethanone uniformly to prepare a precursor solution;

[0044] (2) Pour the precursor solution into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide, and 2 mm high), and irradiate with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure-sensitive adhesive.

[0045] Example 5

[0046] The present embodiment provides a medical pressure-sensitive adhesive and a preparation method thereof, and the preparation method of the medical pressure-sensitive adhesive is as follows:

[0047] (1) Mix 58.11 parts of acrylic acid, 37.13 parts of glycerol, 4.71 parts of epigallocatechin gallate, and 0.05 parts of 2,2-dimethoxy-2-phenylethanone uniformly to prepare a precursor solution;

[0048] (2) Pour the precursor solution into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide, and 2 mm high), and irradiate with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure-sensitive adhesive.

[0049] Example 6

[0050] The present embodiment provides a medical pressure-sensitive adhesive and a preparation method thereof, and the preparation method of the medical pressure-sensitive adhesive is as follows:

[0051] (1) Mix 55.50 parts of acrylic acid, 35.46 parts of glycerol, 8.99 parts of epigallocatechin gallate, and 0.05 parts of 2,2-dimethoxy-2-phenylethanone uniformly to prepare a precursor solution;

[0052] (2) Pour the precursor solution into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide, and 2 mm high), and irradiate with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure-sensitive adhesive.

[0053] Example 7

[0054] The embodiment provides a medical pressure-sensitive adhesive and a preparation method thereof.

[0055] (1) 53.04 parts of acrylic acid, 33.89 parts of glycerol, 13.02 parts of epigallocatechin gallate and 0.05 parts of 2,2-dimethoxy-2-phenylacetophenone are uniformly mixed to prepare a precursor solution;

[0056] (2) The precursor solution is poured into a polytetrafluoroethylene mold (10 cm long, 2.5 cm wide and 2 mm high), and irradiated with 300 W, 365 nm ultraviolet light for 10 min to obtain the medical pressure-sensitive adhesive.

[0057] The medical pressure-sensitive adhesive provided in the above embodiment is subjected to the following performance tests.

[0058] Dry adhesion strength: The medical pressure-sensitive adhesive is cut into a sample with a length of 1.25 cm, a width of 2 cm and a thickness of 0.2 cm, and is attached to the surface of a base material of different materials (the materials are glass, stainless steel, wood, PET, PMMA or PTFE, and the size is 10 cm long, 2 cm wide and 0.2 cm thick). Then, under a load of 50 N, another plate of the same material is immediately pressed onto the surface of the pressure-sensitive adhesive for 5 minutes, a tensile test is performed using a universal testing machine, the tensile rate is 50 mm / min, a total of 3 tests are performed, and the average value is taken.

[0059] Table 1 shows the dry adhesion strength results of the medical pressure-sensitive adhesive.

[0060]

[0061] Wet adhesion strength: The medical pressure-sensitive adhesive is cut into a sample with a length of 1.25 cm, a width of 2 cm and a thickness of 0.2 cm, and is attached to the surface of a base material of different materials (the materials are glass, stainless steel, wood, PET, PMMA or PTFE, and the size is 10 cm long, 2 cm wide and 0.2 cm thick). Then, two drops of deionized water are dropped on the surface of the pressure-sensitive adhesive to wet the surface, under a load of 50 N, another plate of the same material is immediately pressed onto the surface of the pressure-sensitive adhesive for 5 minutes, a tensile test is performed using a universal testing machine, the tensile rate is 50 mm / min, a total of 3 tests are performed, and the average value is taken.

[0062] Table 2 shows the wet adhesion strength results of the medical pressure-sensitive adhesive.

[0063]

[0064]

[0065] From the test results of Table 1 and Table 2, it can be seen that the medical pressure-sensitive adhesive prepared in Examples 1-7 has an adhesion strength of 95-232 kPa to glass, 72-203 kPa to PET, 70-202 kPa to iron, 83-179 kPa to PMMA, 21-83 kPa to PTFE, and 18-55 kPa to pigskin in dry conditions. The medical pressure-sensitive adhesive prepared in Examples 1-7 has an adhesion strength of 18-167 kPa to glass, 12-145 kPa to PET, 15-143 kPa to iron, 11-135 kPa to PMMA, 6-60 kPa to PTFE, and 2-30 kPa to pigskin in humid conditions.

[0066] From the comparison of the dry / wet adhesion strength of Examples 1-7, it can be seen that when the medical pressure-sensitive adhesive contains the epigallocatechin gallate component, the adhesion strength in humid conditions only has a slight decrease compared to the dry adhesion strength, while when the medical pressure-sensitive adhesive only contains the polyacrylic acid and glycerol components, the wet adhesion strength decreases significantly, indicating that the epigallocatechin gallate improves the adhesion performance of the pressure-sensitive adhesive.

[0067] The evaluation of the long-acting antibacterial property of the medical pressure-sensitive adhesive is as follows.

[0068] The medical pressure-sensitive adhesive prepared in the examples is subjected to antibacterial property evaluation by the surface contact method. Staphylococcus aureus and Escherichia coli are diluted into a bacterial suspension of 1 x 10 7 CFU / ml, 10 μl of the bacterial solution is inoculated on the surface of the pressure-sensitive adhesive, then incubated in a 37°C incubator for 3 h, and diluted with 990 μl of physiological saline. 50 μl of the bacterial solution is used to coat a culture dish, and after incubation in a 37°C incubator for 18 h, the colonies are counted to calculate the antibacterial rate.

[0069] Table 3 Antibacterial effect test of medical pressure-sensitive adhesive

[0070]

[0071] The biocompatibility evaluation of the medical pressure-sensitive adhesive is mainly carried out from two dimensions of cell compatibility (CCK-8 cell viability experiment) and blood compatibility (hemolysis test), and the test methods are as follows.

[0072] CCK-8 cell viability experiment: sterilized 1-7# pressure-sensitive adhesive samples are immersed in a basic culture medium and incubated in a cell incubator for 48 h to prepare an extract. Then the extract is centrifuged and filtered to obtain a final extract for cell culture. Mouse fibroblast (L929) cells are seeded in a 96-well plate at a concentration of 1 x 10 5The concentration of CFU was prepared into a cell suspension in complete medium. Next, 100 μL of the cell suspension was inoculated into a 96-well plate and incubated in a cell incubator for 12 hours to allow the cells to adhere. Subsequently, 100 μL of the extraction solution was added and the cells were further incubated for 72 hours. 100 μL of 10% CCK-8 solution was added to the PBS control group and the 1-7# pressure-sensitive adhesive sample group. The cells were then incubated in a cell incubator for 3 hours. The optical density (OD) value was measured at 450 nm using a microplate reader. The cell viability calculation formula was OD 对照组 The ratio of OD 样品组 , and the average value was taken from three tests.

[0073] Hemolysis test: The rat blood was diluted 5 times with PBS, and then the diluted blood was incubated with the 1-7# pressure-sensitive adhesive sample in an incubator at 37°C for 30 minutes. After incubation, the supernatant was centrifuged at 3000 rpm for 10 minutes, and then transferred to a 96-well plate. Ultrapure water and blood diluted with PBS were used as positive and negative controls, respectively. The absorbance (OD) value of the supernatant at 540 nm was measured using a microplate reader, and the hemolysis rate was calculated according to the formula (OD 样品组 -OD 阴性对照组 ) / (OD 阳性对照组 -OD 阴性对照组 ), and the average value was taken from three tests.

[0074] Table 4 Pressure-sensitive adhesive biocompatibility test

[0075]

[0076] As can be seen from the test results in Tables 3-4, Examples 5-7 exhibit excellent antibacterial performance and good biocompatibility. This indicates that the introduction of the epigallocatechin gallate component can produce a synergistic effect with other components, thereby significantly improving the antibacterial performance and biocompatibility of the material.

[0077] The applicant states that the process of the present application is illustrated by the above examples, but the present application is not limited to the above process steps, i.e. it does not mean that the present application must rely on the above process steps to be implemented. It should be understood by those skilled in the art that any improvement on the present application, equivalent replacement of the materials selected by the present application, addition of auxiliary ingredients, selection of specific methods, etc. fall within the scope of protection and disclosure of the present application.

Claims

1. A medical pressure-sensitive adhesive, characterized in that: The raw materials for preparing the medical pressure-sensitive adhesive include acrylic acid, glycerol, epigallocatechin gallate and a photoinitiator.

2. A medical pressure-sensitive adhesive according to claim 1, characterized in that: The medical pressure-sensitive adhesive is prepared by UV-induced polymerization of acrylic acid to form polyacrylic acid, which is then cross-linked with glycerol and epigallocatechin gallate via hydrogen bonding. The polypropylene and glycerol are hydrophilic, absorbing water molecules from the wound tissue surface. Epigallocatechin gallate then adheres tightly to the wound using its adhesive properties. Furthermore, glycerol and epigallocatechin gallate exhibit excellent antibacterial and anti-inflammatory properties, with the two active substances acting synergistically to accelerate tissue wound healing.

3. A medical pressure-sensitive adhesive according to claim 1, characterized in that: The raw material ratios for preparing the medical pressure-sensitive adhesive (total amount is 100 parts) are: 10-78 parts of acrylic acid, 20-88 parts of glycerol, 0-15 parts of epigallocatechin gallate and 0.01-0.1 parts of photoinitiator.

4. A medical pressure-sensitive adhesive according to claim 3, characterized in that: 50-60 parts of acrylic acid, 30-38 parts of glycerol, 4-14 parts of epigallocatechin gallate and 0.04-0.06 parts of photoinitiator.

5. A medical pressure-sensitive adhesive according to claim 3, characterized in that: 55.50 parts of acrylic acid, 35.46 parts of glycerol, 8.99 parts of epigallocatechin gallate and 0.05 part of 2,2-dimethoxy-2-acetophenone.

6. The method for preparing a medical pressure-sensitive adhesive according to any one of claims 1 to 5, characterized in that: The steps include: (1) mixing acrylic acid, glycerol, epigallocatechin gallate, and a photoinitiator in a weight ratio to prepare a precursor solution; (2) pouring the precursor solution into a polytetrafluoroethylene mold and curing it under ultraviolet light to obtain the medical pressure-sensitive adhesive.

7. The method according to claim 6, characterized in that The photoinitiator includes any one or a combination of at least two of 1-hydroxycyclohexyl benzophenone, 2-hydroxy-2-methyl-1-phenylpropanone, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, or benzophenone and 2,2-dimethoxy-2-phenylacetophenone.

8. The method according to claim 6, characterized in that The wavelength of the ultraviolet light in the ultraviolet light curing is 254-405 nm.

9. The method according to claim 6, characterized in that The UV curing time is 5-10 minutes.

10. The medical pressure-sensitive adhesive according to any one of claims 1 to 5, wherein the medical pressure-sensitive adhesive is used in the preparation of materials for wound dressing, surgical film, indwelling needle fixation and stoma infection prevention.

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