Sodium lipoate-based aggregate biological adhesive and preparation method thereof

Abstract

According to the sodium lipoate-based agglomerate biological adhesive and the preparation method thereof, the local concentration of sodium lipoate in the agglomeration process is improved, so that a five-membered ring disulfide bond of sodium lipoate can be opened to initiate a polymerization reaction, and a strong bidentate salt bridge hydrogen bond can be formed between sodium polylipoate and guanidyl monomer molecules to effectively reduce the potential energy of a system; therefore, the aggregate can be stable for a long time at room temperature and can form a transparent amorphous patch after the solvent is volatilized. Based on the hydrophobicity of a condensation body, the mobility of a polymer chain and abundant guanidyl and carboxylate radical groups on a skeleton of the condensation body, the adhesive can realize long-term stable adhesion to wet tissues such as skin and the like.

Description

Technical Field

[0001] The invention belongs to the field of polymer materials, and in particular relates to a sodium lipoic acid-based coacervate bioadhesive and a preparation method thereof. Background Art

[0002] As an endogenous antioxidant monomer in the human body, lipoic acid (LA) can participate in aerobic metabolism in animals through reactions such as disulfide bond reduction. At the same time, LA can form polymers by initiating ring-opening self-polymerization (ROP) through dynamic disulfide bond exchange in the ethanol phase due to the solvation effect. However, PLA is metastable at room temperature and is easily affected by active terminal sulfur free radicals to induce reverse closed-loop depolymerization into small molecular monomers or oligomers. Although there are many reports that prove that polylipoic acid can be stabilized by multiple covalent cross-linking of polyvinyl monomers, metal ions or ionic liquid complexation, most of the prepared elastomers are difficult to be injectable and have poor biocompatibility. Although sodium polylipoic acid can be prepared by volatile solvents, it is difficult to be stable for a long time due to the presence of its dynamic disulfide bonds and sodium carboxylate salts, and it is not adhesive. Summary of the invention

[0003] The object of the present invention is to overcome the deficiencies of the prior art and provide a sodium lipoate-based coacervate bioadhesive and a preparation method thereof. Sodium lipoate and guanidine structure substances (for example, lauroyl arginine ethyl ester hydrochloride and polyhexamethylene biguanide hydrochloride) are used as raw materials, and the sodium lipoate-based coacervate adhesive is obtained by dissolving the monomer powder into an aqueous solution at different concentrations and mixing equal volumes and fully vortexing. In the adhesive, the strong electron-withdrawing property of the carboxylate structure at the end of sodium lipoate enables it to form a strong bidentate salt bridge hydrogen bond with the guanidine group on the micelle in the guanidine structure monomer solution, thereby condensing and settling in water to form a coacervate adhesive, and by regulating the ratio between the two, the hydrophobicity and adhesion strength of the material can be changed. The comprehensive performance of the sodium lipoate-based coacervate polymer bioadhesive is described by multiple aspects such as the adhesive structure and adhesion performance.

[0004] The purpose of the present invention is achieved through the following embodiments:

[0005] A sodium lipoate-based coacervate bioadhesive comprises sodium lipoate and a guanidine-based structure substance, which coagulates and settles in water to form a coacervate adhesive; a salt bridge hydrogen bond is formed between the carboxylate structure at the end of the sodium lipoate and the guanidine group of the guanidine-based structure substance; the guanidine-based structure substance is a guanidine-based structure monomer or a guanidine-based structure polymer.

[0006] The mass ratio of sodium lipoate to the guanidine structure monomer is (1-5):3, preferably (8-24):15, and the guanidine structure monomer is lauroyl arginine ethyl ester hydrochloride.

[0007] The mass ratio of sodium lipoate to the guanidine structure polymer is (1-3):3, preferably (2-3):3, and the guanidine structure polymer is polyhexamethylene biguanide hydrochloride.

[0008] In the adhesive of the present invention, the ratio between sodium lipoate and guanidine structure substance is regulated to adjust and / or change the properties of the material, such as hydrophobicity, adhesion strength, rheological properties, etc.

[0009] During the preparation, the sodium lipoic acid aqueous solution and the guanidine structure substance aqueous solution are mixed and then vortexed, and after the supernatant is removed, the mixture is condensed and precipitated to form an aggregate adhesive.

[0010] During the preparation, equal volumes of sodium lipoate aqueous solution and guanidine structure substance aqueous solution are fully vortexed for 1-5 minutes, preferably 2-3 minutes.

[0011] During the preparation, the concentration of the aqueous solution of the guanidine structure substance is kept constant, and the concentration of the sodium lipoic acid aqueous solution is adjusted to obtain coagulant adhesives of different proportions.

[0012] The invention has a simple preparation method, a wide range of material sources and strong practicality. Sodium lipoic acid forms micelles in a solution with a monomer or polymer with a guanidine structure, such as lauroyl arginine ethyl ester hydrochloride and polyhexamethylene biguanide hydrochloride, etc., and forms a double salt bridge hydrogen bond between the guanidine group and the carboxylate anion, thereby condensing and settling from the aqueous solution to form a biological tissue adhesive with excellent water resistance and long-term stable adhesion to biological tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 The XRD spectra of sodium lipoate, lauroyl arginine ethyl ester hydrochloride monomers and coacervate polymers PLANa-LAE-x with different compositions in the present invention are shown.

[0014] Figure 2 The graph is a test result of the adhesion strength of adhesives of different compositions in the present invention to pig skin tissue at 90% relative humidity.

[0015] Figure 3 Graph showing rheological test results of adhesives with different compositions in the present invention. DETAILED DESCRIPTION

[0016] The technical solution of the present invention is further described below in conjunction with specific examples. The present invention is further described below in conjunction with examples, but these examples are not intended to limit the present invention.

[0017] Aqueous solutions with sodium lipoate concentrations of 0.08, 0.12, 0.16, 0.20, and 0.24 g / mL were prepared, and mixed with 0.15 g / mL aqueous solution of guanidine structure monomer (taking lauroyl arginine ethyl ester hydrochloride aqueous solution as an example), and vortexed and mixed with equal volumes for 2 minutes, and then the supernatant was removed to obtain the PLANa-LAE-x coacervate adhesive.

[0018] Solutions with sodium lipoate concentrations of 0.1000, 0.1125, 0.1250, 0.1375, and 0.1500 g / mL were prepared, mixed with equal volumes of 0.15 g / mL guanidine structure monomer solution (taking polyhexamethylene biguanide hydrochloride aqueous solution as an example), vortexed to fully mix and remove the supernatant, and then the PLANa-PHMB-x coacervate adhesive was obtained.

[0019] Wherein, x represents the concentration of sodium lipoate aqueous solution. For example, PLANa-LAE-0.24 is an adhesive obtained by vortex mixing of equal volumes of solutions when the concentration of sodium lipoate is 0.24 g / mL, and PLANa-PHMB-0.1000 is an adhesive obtained by vortex mixing of equal volumes of solutions when the concentration of sodium lipoate is 0.1000 g / mL. The prepared sodium lipoate-based polymer bioadhesives of each component are used for characterization of material structure, adhesion, and testing of basic properties in vivo and in vitro.

[0020] The XRD test method used in this experiment is to use Cu Kα rays at 1°min -1 The crystal structure XRD data of sodium lipoate, lauroyl arginine ethyl ester hydrochloride powder, and PLANa-LAE-x agglomerate were measured at a scanning rate of 5-50° (2θ). For detailed XRD test steps, please refer to the literature—Chunyan Cui, Yage Sun, Xiongfeng Nie, Xuxuan Yang, Fushuo Wang, Wenguang Liu*A Coenzyme-Based Deep Eutectic Supramolecular Polymer Bioadhesive, Advanced Functional Materials, 2023, 2307543.

[0021] The rheological test methods used in this experiment are frequency sweep and shear rate sweep test. Frequency sweep: At 25°C, record the change of G' and G" of the adhesive with frequency, frequency range: 0.05-100Hz; shear strain: 0.1%; shear rate sweep test: In order to characterize the shear thinning behavior of the coagulant adhesive, at 25°C, through steady-state flow test, record the change of ink viscosity with shear rate 0.1-500s -1The detailed rheological test steps can be found in the literature—Ziyang Xu, Chuanchuan Fan, Qian Zhang, Yang Liu, Chunyan Cui, Bo Liu, Tengling Wu, Xiaoping Zhang, Wenguang Liu*A Self-Thickening and Self-Strengthening Strategy for 3D Printing High-Strength and Antiswelling Supramolecular Polymer Hydrogels as Meniscus Substitutes, Advanced Functional Materials, 2021, 31, 2100462.

[0022] The adhesion strength test method used in this experiment is the lap shear method. The cohesive adhesive is extruded and adhered to the wet pigskin surface, and another piece of pigskin is used to adhere the other side. After gently pressing for 10 seconds, the test is immediately carried out. During the test, the two pieces of pigskin are fixed on the tensile machine respectively, and the pigskin is stretched at a certain speed. The stretching speed is 50mm / min. For detailed stretching process steps, please refer to the literature—Chunyan Cui, Chuanchuan Fan, Yuanhao Wu, MengXiao, Tengling Wu, Dongfei Zhang, Xinyu Chen, Bo Liu, Ziyang Xu, Bo Qu, WenguangLiu*Water-Triggered Hyperbranched Polymer UniversalAdhesives:From StrongUnderwater Adhesion to RapidSealing Hemostasis, AdvancedMaterials, 2019, 31, 1905761.

[0023] from Figure 1 It can be seen that the single sodium lipoate and lauroyl arginine ethyl ester hydrochloride monomers are highly crystalline, but in the structure of PLANa-LAE-X, the crystallization peaks of sodium lipoate and lauroyl arginine ethyl ester hydrochloride monomers all disappear and a broad peak appears at 20.2°, indicating that sodium lipoate polymerizes and exists stably in the condensate system without depolymerization. Continuing to increase the content of sodium lipoate, there are no other diffraction peaks, proving that lauroyl arginine ethyl ester hydrochloride has a good stabilizing effect on it.

[0024] Figure 2 The following is a graph showing the adhesion strength test results of different adhesive compositions on pig skin tissue at 90% relative humidity. a is the instantaneous adhesion strength of different composition PLANa-LAE-x adhesives on pig skin tissue, b is the instantaneous adhesion strength of different composition PLANa-PHMB-x adhesives on pig skin tissue, and c is the adhesion strength curve of PLANa-LAE-0.24 on pig skin tissue at 90% relative humidity over time. From the results, it can be seen that the instantaneous adhesion strength of the adhesive shows an overall upward trend with the increase of sodium lipoic acid concentration, indicating that the bulk strength of the adhesive is very critical in its adhesion performance, and the cohesive strength of the adhesive will increase with its monomer concentration. We also tested the adhesion strength of the coacervate adhesive prepared from polyhexamethylene biguanide hydrochloride solution and sodium lipoate solution. The coacervate adhesive formed by polyhexamethylene biguanide hydrochloride gradually changed from bulk damage to interfacial damage during the stretching process as the concentration of sodium lipoate increased, indicating that the bidentate hydrogen bond density formed by polyhexamethylene biguanide hydrochloride and sodium lipoate was higher, and the interaction between the components was relatively stronger, so the bulk strength of the adhesive was higher. For this reason, after curing, PLANa-PHMB-x was different from PLANa-LAE-x coacervate adhesive and no longer had adhesion. As time went on, the molecular chains of PLANa-LAE-x coacervate adhesive were further arranged and reorganized on the adhesive substrate, and the cohesive strength of the adhesive was further improved with the evaporation of water, and the maximum adhesion strength could reach 18.3kPa.

[0025] Figure 3 The following are the rheological test results of adhesives with different compositions, a is the frequency scanning curve of PLANa-LAE-x adhesives with different compositions, and b is the viscosity-shear rate curve of adhesives with different compositions. It can be seen from the results that as the concentration of sodium lipoate increases, the viscosity of the adhesive increases accordingly. When the concentration of sodium lipoate is higher than 0.16 g / mL, the viscosity of the coagulation is significantly improved. This is because the increase in the concentration of sodium lipoate monomer solution can cause self-polymerization, thereby significantly improving its cohesive strength; as the shear rate increases, the viscosity of the adhesive shows a downward trend.

[0026] According to the content of the present invention, the process parameters are adjusted to achieve the preparation of the adhesive, and the performance is basically consistent with the present invention after testing. The above is an exemplary description of the present invention. It should be noted that any simple deformation, modification or equivalent replacement that can be made by other technicians in this field without spending creative labor falls within the protection scope of the present invention without departing from the core of the present invention.

Claims

1. A sodium lipoic acid based coacervate bioadhesive, characterized in that: The invention comprises sodium lipoic acid and a guanidine structure substance, which coagulate and precipitate to form a coagulation adhesive, wherein a salt bridge hydrogen bond is formed between the carboxylate structure at the end of sodium lipoic acid and the guanidine group of the guanidine structure substance, and the guanidine structure substance is a guanidine structure monomer or a guanidine structure polymer.

2. A sodium lipoic acid based coagulant bioadhesive according to claim 1, characterized in that: The performance of the material can be adjusted and / or changed by regulating the ratio between sodium lipoic acid and the guanidine structural substance.

3. A sodium lipoic acid based coagulant bioadhesive according to claim 1 or 2, characterized in that: The mass ratio of sodium lipoate to the guanidine structure monomer is (1-5):3, and the guanidine structure monomer is lauroyl arginine ethyl ester hydrochloride.

4. A sodium lipoic acid based coacervate bioadhesive according to claim 1 or 2, characterized in that: The mass ratio of sodium lipoate to the guanidine structure monomer is (8-24):15, and the guanidine structure monomer is lauroyl arginine ethyl ester hydrochloride.

5. A sodium lipoic acid based coagulant bioadhesive according to claim 1 or 2, characterized in that: The mass ratio of sodium lipoate to the guanidine structure polymer is (1-3):3, and the guanidine structure polymer is polyhexamethylene biguanide hydrochloride.

6. A sodium lipoic acid based coacervate bioadhesive according to claim 1 or 2, characterized in that: The mass ratio of sodium lipoate to the guanidine structure polymer is (2-3):3, and the guanidine structure polymer is polyhexamethylene biguanide hydrochloride.

7. A method for preparing a sodium lipoic acid-based coacervate bioadhesive, characterized in that: The sodium lipoic acid aqueous solution and the guanidine structure substance aqueous solution are mixed and vortexed, and after the supernatant is taken out, the mixture is condensed and precipitated to form a coagulated adhesive; the guanidine structure substance is a guanidine structure monomer or a guanidine structure polymer.

8. The method for preparing a sodium lipoic acid-based coagulant bioadhesive according to claim 7, characterized in that: The concentration of the aqueous solution of the guanidine structure substance is kept constant, and the concentration of the sodium lipoic acid aqueous solution is adjusted to obtain coacervate adhesives with different proportions.

9. The method for preparing a sodium lipoic acid-based coagulant bioadhesive according to claim 7, characterized in that: Vortex the sodium lipoate aqueous solution and the guanidine structure substance aqueous solution in equal volumes for 1-5 minutes.

10. The method for preparing a sodium lipoic acid-based coagulant bioadhesive according to claim 7, characterized in that: Vortex the sodium lipoate aqueous solution and the guanidine structure substance aqueous solution in equal volumes for 2-3 minutes.

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