Wet environment induced adhesion polylipoic acid-based elastic patch as well as preparation method and application thereof

Abstract

The invention discloses a polylipoic acid-based elastic patch capable of inducing adhesion in a wet environment as well as a preparation method and application of the polylipoic acid-based elastic patch. The polylipoic acid-based elastic adhesion patch can be obtained by simply concentrating and evaporating a mixed solution of lipoic acid and methacrylated gelatin. Due to the introduction of a methacrylated gelatin polymer chain, the layered crystal structure of an original lipoic acid-based polymer is reduced, so that the water sensitivity of the lipoic acid-based polymer is reduced, the release time of lipoic acid active molecules is prolonged, and a small amount of layered crystal structures are reserved in the polylipoic acid-based elastic adhesion patch; therefore, non-adhesion and rigidity are realized in a dry environment. Once exposed to water or body fluid, the hydrophilic polymer backbone of the patch can quickly absorb moisture, the entry of water molecules destroys the layered crystal structure, resulting in softness and adhesion of the patch. In a rat model with ligation of periodontitis, the patch can effectively relieve inflammation and inhibit alveolar bone resorption.

Description

Technical Field

[0001] The present invention belongs to the field of polymer materials, and particularly relates to a polythioctic acid-based elastic patch induced by wet state environment for adhesion, and a preparation method and application thereof. Background Art

[0002] The periodontal tissue, including soft tissue (gingiva and periodontal ligament) and hard tissue (cementum and alveolar bone), plays a key role in fixing teeth and transmitting chewing force. Periodontitis is the most common periodontal disease, which is essentially a chronic inflammatory disease caused by pathogenic bacteria, leading to alveolar bone resorption and tooth loosening and falling out, seriously reducing the quality of life of patients. Periodontal scaling or regenerative periodontal surgery (such as bone grafting combined with antibiotic-assisted treatment) is the most commonly used method for treating periodontitis clinically. However, due to the complexity of the periodontal pocket structure and the concealment of its location, as well as the drug resistance of antibiotics, this traditional treatment method cannot effectively treat periodontitis and may cause great trauma to patients. In addition, due to the high humidity and dynamic characteristics of the oral cavity, antibiotics are difficult to stay near the periodontium continuously, which further reduces the treatment efficiency. Therefore, it is still urgent to develop an efficient and non-invasive treatment strategy for periodontitis.

[0003] The wet tissue adhesive with a three-dimensional network can help the controlled release of drugs or cytokines, and accelerate the regeneration and remodeling of periodontal tissue. Among them, the injectable viscous hydrogel for the treatment of periodontitis has been widely reported because it can be accurately injected into the periodontal pocket. However, the gelation of many injectable viscous hydrogels requires the assistance of light or heat, which increases the complexity of the operation. In addition, when the uncrosslinked hydrogel precursor solution is injected into the periodontal pocket, it may diffuse into the tissue and cause tissue inflammation. The viscous patch can solve these problems of the injectable adhesive hydrogel, but many reported viscous patches often show reduced adhesion or adhesion loss, poor biocompatibility and non-degradability when used in a humid and dynamic environment, which also limits its application in the oral cavity. In addition, most of the periodontitis treatment materials lack intrinsic treatment ability. Although exogenous drugs, cytokines or proteins can regulate the microenvironment of periodontitis and accelerate the regeneration of periodontal tissue, this will also increase the treatment cost or cause potential drug toxicity. Therefore, there is an urgent need to develop a bioactive wet tissue adhesive patch that does not require additional drugs, has low cost, is easy to deliver and is biocompatible to accelerate the healing of periodontitis.

[0004] α-Lipoic acid (LA) is an endogenous small molecule coenzyme in mitochondria, which participates in mitochondrial activity and regulates energy metabolism. Based on the disulfide heterocycle in its structure, LA exhibits excellent antioxidant and anti-inflammatory capabilities and has been proven to have therapeutic effects in various oxidative stress models. Previous studies have also shown that LA can effectively inhibit periodontal bone loss. In addition, based on the characteristics of dynamic ring-opening polymerization (ROP) of sulfur-containing five-membered rings and abundant adhesive carboxyl groups, LA has been used to prepare adhesives. However, due to the reverse ring-opening depolymerization induced by terminal reactive free radicals, the polymerized poly(lipoic acid) (PolyLA) is metastable. Although PolyLA-based polymers can be stabilized by introducing multiple double-bond small molecules or high-concentration ions, the addition of toxic small molecules and ions will significantly reduce the biocompatibility of PolyLA-based polymers. The hydrophobicity of the PolyLA structure also limits the release of LA-based small molecules, sacrificing the biological activity of LA. Recently, it was reported that sodium poly(lipoic acid) (PolyLA-Na) was prepared by simple solvent evaporation, but PolyLA-Na exhibits water-sensitive dissociation behavior when in contact with water. In this case, the dissociation rate of PolyLA-Na is very fast, but its fast dissociation rate (<20 min), non-adhesion, and rigidity limit its application in the biomedical field. Summary of the Invention

[0005] The present invention overcomes the deficiencies in the prior art and provides a poly(lipoic acid)-based elastic patch with wet-state environment-induced adhesion, its preparation method and application. Using lipoic acid monomer and methacrylated gelatin as raw materials, a poly(lipoic acid)-based adhesive patch is obtained by evaporating the mixed solution of the two raw materials. In this adhesive patch, the introduction of GelMA polymer chains reduces the layered crystal structure of the original PolyLA-based polymer, thereby reducing the water sensitivity of the PolyLA-based polymer and prolonging the release time of LA-based active molecules; in addition, the hydrophilic polymer backbone of PolyLA-GelMA can quickly absorb water, and the entry of water molecules destroys the layered crystal structure, making the patch soft and adhesive, and thus achieving the purpose of in vivo application.

[0006] The object of the present invention is achieved by the following technical solutions.

[0007] A polylipoic acid-based elastic patch induced by wet environment adhesion and a preparation method thereof, wherein tris(hydroxymethyl)aminomethane (Tris base), lipoic acid monomer and methacryloyl gelatin are dissolved in water and fully dissolved, the mixed solution is placed at 60-70°C and stirred for 1-3 hours to fully mix, and the mixed solution is placed at 50-60°C and dried to obtain a polylipoic acid-based elastic adhesive patch (PolyLA-GelMA patch), wherein the ratio of methacryloyl gelatin to lipoic acid monomer is 5-75%, the amount of tris(hydroxymethyl)aminomethane is 0.5-1.0g, and the amount of water is 10-20mL.

[0008] The ratio of methacryloyl gelatin to lipoic acid monomer is 25%, the amount of tris(hydroxymethyl)aminomethane is 0.8g, and the amount of water is 15mL.

[0009] The above mixed solution was placed at 65°C and stirred for 2 hours to make it fully mixed, and the above mixed solution was placed at 55°C and dried.

[0010] In the preparation scheme, the mass of Tris base and lipoic acid used remains unchanged, and the mass ratio between lipoic acid and methacryloyl gelatin is changed to obtain adhesive patches with different ratios. The obtained adhesive patches are named PolyLA-GelMA-x, where x represents the mass percentage of methacryloyl gelatin and lipoic acid. For example, PolyLA-GelMA-5 is an adhesive patch obtained by concentration and evaporation when the mass ratio of methacryloyl gelatin to lipoic acid is 5%.

[0011] Application of a polylipoic acid-based elastic patch induced to adhere in a wet environment in a tissue adhesive, a tissue adhesive, especially a wet tissue adhesive, and a wet tissue adhesive, especially a periodontal tissue adhesive.

[0012] The adhesion strength of the polylipoic acid-based elastic adhesive patch is 6.9-28.8kPa. The tensile stress of the polylipoic acid-based elastic adhesive patch decreases with the increase of water absorption. The tensile stress of the polylipoic acid-based elastic adhesive patch is 0.5-2.8MPa. After the polylipoic acid-based elastic adhesive patch is combined with the drug, it can maintain drug release for 7 days.

[0013] The beneficial effects of the present invention are as follows: During the solvent evaporation process, LA undergoes spontaneous ring-opening polymerization to form PolyLA, and the double bonds on GelMA can react with the free radicals at the ends of PolyLA to prevent the depolymerization of PolyLA. The multiple hydrogen bonds formed between the amino groups on GelMA and the carboxyl groups on PolyLA further stabilize PolyLA. In addition, the introduction of GelMA polymer chains reduces the lamellar crystal structure of the original PolyLA-based polymer, thereby reducing the water sensitivity of the PolyLA-based polymer and prolonging the release time of LA active molecules. A small amount of lamellar crystal structure is retained in the PolyLA-GelMA patch, resulting in non-adhesiveness and rigidity in a dry environment. Once exposed to water or body fluids, the hydrophilic polymer backbone of PolyLA-GelMA can rapidly absorb water, and the entry of water molecules destroys the lamellar crystal structure, causing the PolyLA-GelMA patch to become soft and adhesive. Due to the formation of multiple hydrogen bonds and electrostatic interactions between the carboxyl groups on the PolyLA-GelMA patch and the amino groups on the tissue surface, the PolyLA-GelMA patch exhibits rapid, firm, and long-lasting adhesion to moist periodontal tissues. In a rat model of ligature-induced periodontitis, the PolyLA-GelMA patch can effectively relieve inflammation and inhibit alveolar bone resorption. The preparation method of the present invention is simple, the material sources are wide, and the practicability is strong. Description of the Drawings

[0014] Figure 1 are the ultraviolet-visible absorption spectra of (a) LA-GelMA solution and dry PolyLA-GelMA patch; (b) 1H NMR spectra of LA, PolyLA, and PolyLA-GelMA;

[0015] Figure 2 are the ATR-IR spectra of LA, PolyLA-GelMA, and GelMA;

[0016] Figure 3 is the ATR-IR spectrum of PolyLA-GelMA-25 in different humidity states;

[0017] Figure 4 are (a) the tensile stress of PolyLA-GelMA-x in different states; (b) the tensile strain of PolyLA-GelMA-x in different states;

[0018] Figure 5 are the lap shear curves (a) and adhesion strength (b) of the PolyLA-GelMA-x patch and oral mucosa; (c) The PolyLA-GelMA-25 patch can tightly adhere to different parts of the rat oral cavity and withstand tensile movement;

[0019] Figure 6is the monomer release of PolyLA-GelMA-x patch in artificial saliva;

[0020] Figure 7 is the scavenging efficiency of PolyLA-GelMA-x on DPPH radicals (a) and hydroxyl radicals (b);

[0021] Figure 8 is the survival rate of Staphylococcus aureus and Escherichia coli after co-culture with PolyLA-GelMA-x for 24 hours;

[0022] Figure 9 is the cytocompatibility of PolyLA-GelMA-x adhesive patch;

[0023] Figure 10 is the alveolar bone repair effect of periodontitis treated by different methods. Specific Embodiments

[0024] The technical solutions of the present invention will be further described below through specific embodiments.

[0025] Example 1

[0026] Dissolve 0.5 g of tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacrylated gelatin in 10 mL of water and dissolve thoroughly. The mass ratio of methacrylated gelatin to lipoic acid monomer is 5%. Place the above mixed solution at 60 °C and continue stirring for 3 hours to mix thoroughly. Place the above mixture solution at 50 °C and dry it to obtain the polythioctic acid-based elastic adhesive patch PolyLA-GelMA-5.

[0027] Example 2

[0028] Dissolve 0.8 g of tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacrylated gelatin in 15 mL of water and dissolve thoroughly. The mass ratio of methacrylated gelatin to lipoic acid monomer is 25%. Place the above mixed solution at 65 °C and continue stirring for 2 hours to mix thoroughly. Place the above mixture solution at 55 °C and dry it to obtain the polythioctic acid-based elastic adhesive patch PolyLA-GelMA-25.

[0029] Example 3

[0030] Dissolve 1.0 g of tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacrylated gelatin in 20 mL of water and dissolve thoroughly. The mass ratio of methacrylated gelatin to lipoic acid monomer is 75%. Place the above mixed solution at 70 °C and continue stirring for 1 hour to mix thoroughly. Place the above mixture solution at 60 °C and dry it to obtain the polythioctic acid-based elastic adhesive patch PolyLA-GelMA-75.

[0031] Example 4

[0032] 0.6g of tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacryloyl gelatin were dissolved in 12mL of water and fully dissolved. The mass ratio of methacryloyl gelatin to lipoic acid monomer was 50%. The mixed solution was stirred at 63℃ for 2.5 hours to make it fully mixed. The mixed solution was dried at 52℃ to obtain the polylipoic acid-based elastic adhesive patch PolyLA-GelMA-50.

[0033] Example 5

[0034] 0.9g tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacryloyl gelatin were dissolved in 18mL water and fully dissolved. The mass ratio of methacryloyl gelatin to lipoic acid monomer was 10%. The mixed solution was stirred at 68℃ for 1.5 hours to make it fully mixed. The mixed solution was dried at 58℃ to obtain the polylipoic acid-based elastic adhesive patch PolyLA-GelMA-10.

[0035] Test Example

[0036] The polylipoic acid-based elastic adhesive patch of PolyLA-GelMA-25 prepared in Example 2, which is responsive to wet environment and induces adhesion and body softening, is used for characterization of material structure, adhesion, and basic performance testing in vivo and in vitro:

[0037] If Figure 1 As shown in this figure, this figure is a structural characterization of the polylipoic acid-based elastomer adhesive patch that triggers adhesion and bulk softening in response to a wet environment. From the UV spectrum results, it can be seen that after the solvent evaporates to form the PolyLA-GelMA patch, the absorption peak of the five-membered ring of the disulfide bond in the LA monomer in the LA-GelMA solution at 330nm disappears, indicating that LA does spontaneously undergo ring-opening polymerization during the concentration process (a). NMR results also prove the efficient copolymerization reaction of LA and GelMA (b).

[0038] If Figure 2 As shown in this figure, the attenuated total reflection infrared (ATR-IR) spectra of lipoic acid monomer, methacryloyl gelatin and polylipoic acid-methacryloyl gelatin elastomer adhesive patch, it can be seen from the figure that compared with the original LA monomer, the -C=O peak on the carboxylate in the PolyLA-GelMA patch shows an obvious red shift, indicating that the ─COOH in LA and the -NH in GelMA 2 Strong hydrogen bonding interactions occurred between them, which further confirmed the interaction between PolyLA and GelMA in the PolyLA-GelMA patch.

[0039] If Figure 3 ​​As shown, this figure is the infrared spectrum of the polylipoic acid-methacrylated gelatin elastomer adhesive patch under different humidity conditions. As can be seen from the figure, the peak intensity of -COOH gradually increases near 3400 cm -1 , indicating that there is bound water in the polymer network after the patch is placed in 90% RH for different times. After absorbing water, the carboxylic acid groups of PolyLA and the amino groups of GelMA move from 1633 cm -1 and 1537 cm -1 to 1628 cm -1 and -1530 cm -1 , showing a slight red shift, indicating that the carboxylic acid groups and amino groups have undergone hydration.

[0040] As Figure 4 shown, this figure is the tensile stress and strain results of the polylipoic acid-methacrylated gelatin elastomer adhesive patches with different compositions under different humidities. As can be seen from the results, compared with the dry PolyLA-GelMA, the tensile stress of the PolyLA-GelMA patches with different compositions decreases (a) and the elongation increases (b) after being placed in 90% RH for different times. This is because water molecules destroy the layered crystal structure of PolyLA-GelMA. (The mechanical property test method is to cut the prepared polylipoic acid-methacrylated gelatin elastomer adhesive patches with different compositions into rectangles with a cutter, conduct tensile tests through a tensile machine, and record the tensile stress and tensile strain. The tensile speed is 50 mm / min.).

[0041] As Figure 5As shown in the figure, this figure shows the adhesion ability of polythioctic acid-methacrylated gelatin elastomer adhesive patches with different compositions to the rat oral cavity. It can be seen from the results that as the content of GelMA increases, the adhesion strength of the PolyLA-GelMA patch first increases and then decreases (a, b). When the GelMA content is 25%, the adhesion strength reaches the maximum value of 28.9 kPa. The reason is that the introduction of GelMA increases the crosslinking density of the polymer network, thereby enhancing the wet stability and cohesive strength of the patch. When the GelMA content is higher than 25%, the cohesive energy of the patch is greater than the interfacial energy, which is not conducive to removing the hydrated layer on the wet tissue interface and affects the wet adhesion of the patch. PolyLA-GelMA-25 can firmly adhere to the tissue surfaces of the rat cheek, gum, tongue and palate. The PolyLA-GelMA-25 patch was stretched with forceps to simulate oral movements (c). Obviously, the PolyLA-GelMA-25 patch can still adhere to the tissue without falling off, which once again proves the excellent adhesion of PolyLA-GelMA-25 to the oral mucosa. (The adhesion strength test method used in this experiment is the lap shear method. By cutting the adhesion patch into square samples with a size of 10 mm * 10 mm, one side of it is adhered to the surface of the moist oral mucosa, and the other side is adhered with another piece of oral mucosa, and the test is carried out immediately. During the test, the two pieces of oral mucosa are fixed on the tensile machine respectively, and the oral mucosa is stretched at a certain speed. The stretching speed is 50 mm / min.)

[0042] As Figure 6 shown in the figure, this figure shows the monomer release curves of polythioctic acid-methacrylated gelatin elastomer adhesive patches with different ratios. Since PolyLA-GelMA is water-sensitive, it will gradually release lipoic acid monomers when exposed to water. Lipoic acid has excellent antioxidant and antibacterial effects. Therefore, the effective release of lipoic acid monomers is crucial for the in vivo application of the adhesive patch. By immersing the adhesive patch in artificial saliva for different times and then measuring the content of lipoic acid in the saliva, as shown in the figure, the continuous release of lipoic acid active molecules can be achieved in each composition of the patch, and the release amount increases with the increase of the lipoic acid content in the patch. The test method is as follows: Weigh adhesive patches with different compositions into artificial saliva and keep the concentration of the material in the artificial saliva at 2 mg / ml. Place the prepared solution in a constant temperature oven at 37 °C and measure its ultraviolet absorption at different times. The ultraviolet absorption measurement range is 200 - 400 nm. And calculate the release amount of different compositions of materials in artificial saliva at different times through the ultraviolet absorption standard curve of lipoic acid in artificial saliva.

[0043] As Figure 7As shown, based on the excellent antioxidant ability of lipoic acid small molecules, it shows a very good effect of scavenging free radicals. The results are shown in the figure. Due to the efficient release of LA by PolyLA-GelMA, it shows a very good effect of scavenging DPPH free radicals (a) and hydroxyl free radicals (b), which lays a foundation for its in vivo application. (The experimental method for DPPH free radical scavenging test is to incubate 10 mg of PolyLA-GM-x with 0.05 mmol / L DPPH solution in the dark at 37 °C for 12 h, and then measure the absorbance of the supernatant at a wavelength of 517 nm using an ultraviolet-visible spectrophotometer. The control group is a pure DPPH solution under the same conditions. The hydroxyl free radical scavenging ability of the adhesive patch was tested using the Fenton reaction. The specific method is to first mix 600 μL of 2 mmol / L FeSO 4 solution, 500 μL of safranin O solution and 10 mg of the sample and incubate for 10 minutes. Subsequently, 800 μL of H 2 O 2 (6 wt%) solution was added to the above solution and incubated at 55 °C for 30 minutes. 300 μL of ultrapure water was used to replace the sample as the blank group, and 1100 μL of ultrapure water was used to replace the sample and H 2 O 2 was used as the control group. At the predetermined time, the solution was cooled to room temperature, and the absorbance at 492 nm was measured on an enzyme-linked immunosorbent assay (ELISA) reader).

[0044] As Figure 8 shown, based on the excellent antibacterial properties of lipoic acid small molecules, we detected the bactericidal effects of PolyLA-GelMA on Escherichia coli and Staphylococcus aureus. The results are shown in the figure. As the incubation time with bacteria prolonged, the lipoic acid small molecules in the patch were gradually released and then showed bactericidal effects. And after co-culturing with bacteria for 24 h, the bactericidal rate was still up to 80%. (The experimental method for antibacterial test is to mix 1 ml of Escherichia coli or Staphylococcus aureus (10 5 CFU mL -1 ) bacterial suspension with 20 mg of PolyLA-GelMA-x and culture at 37 °C for 24 h. The untreated bacterial suspension was set as the control group. The survival rates of different groups in OD600 were recorded, and the bacterial survival rate was calculated using the OD600 value).

[0045] As Figure 9As shown, this figure shows the cell compatibility of polythioctic acid-methacrylated gelatin elastomeric adhesive patches with different ratios. Polythioctic acid-methacrylated gelatin with different ratios co-cultured with periodontal ligament stem cells at a concentration of 10 μg / mL for 3 days promoted cell proliferation more significantly than at a concentration of 5 μg / mL. In addition, PolyLA-GelMA-25 had the highest cell proliferation rate, followed by PolyLA-GelMA-50 and PolyLA-GelMA-75. This is consistent with the trend of monomer release, indicating that LA is an effective bioactive molecule for promoting cell proliferation.

[0046] As Figure 10 shown, based on the excellent tissue adhesiveness and bioactivity of PolyLA-GelMA-25, it was developed into a tissue adhesive patch for the treatment of periodontitis. In a ligature-induced periodontitis rat model, we found that the polythioctic acid-based adhesive patch could rapidly adhere to the periodontal pocket, resist the oral moist dynamic environment, continuously provide the bioactive molecule LA, relieve periodontal inflammation, inhibit further alveolar bone resorption, and the therapeutic effect was comparable to that of the commercial periodontal ointment, Periochip.

[0047] The above is an exemplary description of the present invention. It should be noted that any simple deformation, modification, or equivalent substitution that can be made by those skilled in the art without creative labor falls within the protection scope of the present invention without departing from the core of the present invention.

Claims

1. A polylipoic acid-based elastic patch induced to adhere in a wet environment, characterized in that: Dissolve tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacryloyl gelatin in water and fully dissolve them, place the mixed solution at 60-70°C and continue stirring for 1-3 hours to fully mix them, and place the mixed solution at 50-60°C for drying to obtain a polylipoic acid-based elastic adhesive patch, wherein the ratio of methacryloyl gelatin to lipoic acid monomer is 5-75%, the amount of tris(hydroxymethyl)aminomethane is 0.5-1.0g, and the amount of water is 10-20mL.

2. A polylipoic acid-based elastic patch induced to adhere in a wet environment according to claim 1, characterized in that: The usage ratio of methacryloyl gelatin and lipoic acid monomer is 25%, the usage of tris(hydroxymethyl)aminomethane is 0.8 g, and the usage of water is 15 mL.

3. The polylipoic acid-based elastic patch with induced adhesion in a wet environment according to claim 1, characterized in that: The mixed solution was placed at 65°C and stirred for 2 hours to make it fully mixed, and the mixed solution was placed at 55°C for drying.

4. A method for preparing a polylipoic acid-based elastic patch induced to adhere in a wet environment as claimed in any one of claims 1 to 3, characterized in that: Dissolve tris(hydroxymethyl)aminomethane, lipoic acid monomer and methacryloyl gelatin in water and fully dissolve them, place the mixed solution at 60-70°C and continue stirring for 1-3 hours to fully mix them, and place the mixed solution at 50-60°C for drying to obtain a polylipoic acid-based elastic adhesive patch, wherein the ratio of methacryloyl gelatin to lipoic acid monomer is 25%, the amount of tris(hydroxymethyl)aminomethane is 0.8g, and the amount of water is 15mL.

5. The method for preparing a polylipoic acid-based elastic patch induced to adhere in a wet environment according to claim 4, characterized in that: The usage ratio of methacrylylated gelatin and lipoic acid monomer is 5-75%, the usage of tris(hydroxymethyl)aminomethane is 0.5-1.0 g, and the usage of water is 10-20 mL.

6. The method for preparing a polylipoic acid-based elastic patch with induced adhesion in a wet environment according to claim 4, characterized in that: The mixed solution was placed at 65°C and stirred for 2 hours to make it fully mixed, and the mixed solution was placed at 55°C for drying.

7. Use of the polylipoic acid-based elastic patch induced to adhere in a wet environment as claimed in claim 1 in a tissue adhesive.

8. The use according to claim 7, characterized in that: The tissue adhesive is particularly a wet tissue adhesive.

9. The use according to claim 8, characterized in that: Wet tissue adhesives are particularly suitable for periodontal tissue adhesives.

10. The use according to claim 9, characterized in that: The adhesion strength of the polylipoic acid-based elastic adhesive patch is 6.9-28.8 kPa, and the tensile stress of the polylipoic acid-based elastic adhesive patch decreases with the increase of water absorption. The tensile stress of the polylipoic acid-based elastic adhesive patch is 0.5-2.8 MPa. After the polylipoic acid-based elastic adhesive patch is combined with the drug, it can maintain drug release for 7 days.

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