CN113621342B

CN113621342B - Solvent-free binder and preparation method and application thereof

Info

Publication number: CN113621342B
Application number: CN202110994309.7A
Authority: CN
Inventors: 李建树; 罗珺; 柯翔; 唐术衔; 董知韵
Original assignee: Sichuan University
Current assignee: Sichuan University
Priority date: 2021-08-27
Filing date: 2021-08-27
Publication date: 2022-08-26
Anticipated expiration: 2041-08-27
Also published as: CN113621342A

Abstract

The invention discloses a solvent-free binder and a preparation method and application thereof, wherein the binder comprises the following raw material components: lipoic acid and/or derivatives thereof, polyphenol compounds and inorganic iron salts. The preparation method forms the lipoic acid or/and the derivatives thereof, the polyphenol compound and the inorganic iron salt into the viscous-state solvent-free binder with good universality binding performance by one-step high-temperature self-polymerization and cross-linking of non-covalent bonds and metal coordination bonds.

Description

Solvent-free binder and preparation method and application thereof

Technical Field

The invention relates to the technical field of adhesives.

Background

At present, the use of adhesives is becoming more widespread and important in the fields of light industry, aviation, electronics and medicine, and higher requirements are also placed on the ease of use and the stability of properties in dry/wet environments. Particularly in the medical field, in order to heal wounds and prevent leakage of body fluid or blood, a surgical suture line and a staple suture mode are mostly adopted in clinic, but the two modes are easy to cause wound inflammation, meanwhile, the operation is long in time consumption and inconvenient in minimally invasive positions, and due to the fact that an adhesive comes out, the defects that the traditional suture line and the staple are used for wound healing are greatly overcome.

However, in the prior art, a common resin adhesive needs to be cured/crosslinked under external stimulation, mixing or in-situ preparation conditions to exert viscosity, and has the problems of poor biological safety and bonding effect, incapability of adopting an injection mode for delivery and the like, for example, although the traditional adhesive alpha-cyanoacrylate has high viscosity, the traditional adhesive is easy to cure and harden after bonding, and meanwhile, a degradation product has toxicity, so that the characteristics increase the complexity of the using process of the adhesive and limit the application of the adhesive; on the other hand, although a part of the adhesive has better biocompatibility, the adhesive has the problems of non-adhesion when meeting water or poor adhesion effect under water, and the like, for example, although the fibrin glue has better biocompatibility, the adhesive property of the fibrin glue is obviously reduced under the wet environment of body fluid, the expected adhesive effect cannot be achieved, and although the problems can be improved by means of bonding by using a special bionic hydrogel adhesive under the wet environment, the defects that the special adhesive loses adhesion stability due to water loss in a dry environment or freezing under a low-temperature environment and the like can also exist; in addition, the existing adhesive has the defects of poor antibacterial effect, easy infection and inflammation initiation in the wound healing process and the like; the above problems all limit the wide application of adhesives in the medical field.

Disclosure of Invention

The invention aims to provide an adhesive which has good biocompatibility and antibacterial performance, no toxic or side effect and toxic by-products, does not contain solvent and can be well bonded in various environments, particularly wet environments, and a preparation method and some effective applications of the adhesive.

The invention firstly discloses the following technical scheme:

a solvent-free binder comprises the following raw material components: lipoic acid and/or derivatives thereof, polyphenol compounds and inorganic iron salts.

According to some preferred embodiments of the present invention, the polyphenol compound is selected from one or more of tannic acid, ellagic acid, epigallocatechin gallate, procyanidins, gallic acid, pyrogalloc acid.

According to some preferred embodiments of the invention, the inorganic iron salt is selected from iron trichloride and/or iron sulfate.

According to some preferred embodiments of the present invention, the mass of the polyphenol compound is 0.1 to 20% of the mass of the lipoic acid and/or derivatives thereof.

According to some preferred embodiments of the present invention, the molar ratio of the lipoic acid and/or derivatives thereof to the inorganic iron salt is (10-200): 1.

The invention further provides a preparation method of the solvent-free binder, which comprises the following steps:

(1) melting lipoic acid and/or derivatives thereof at 60-200 ℃;

(2) adding a polyphenol compound into the melt obtained in the step (1) for mixing, and forming a uniform mixed melt at the temperature of 60-200 ℃;

(3) adding inorganic ferric salt into the mixed melt obtained in the step (2) for mixing, and forming a uniform mixed melt at the temperature of 60-200 ℃;

(4) and (4) standing and cooling the mixed melt obtained in the step (3) to room temperature to obtain the solvent-free binder.

Under this preparation method, some preferred embodiments are as follows:

the polyphenol compound is selected from one or more of tannic acid, ellagic acid, epigallocatechin gallate, procyanidin, gallic acid, and pyrogalloc acid.

The inorganic ferric salt is selected from ferric trichloride and/or ferric sulfate.

The mass of the polyphenol compound is 0.1-20% of the mass of the lipoic acid and/or the derivative thereof, and the molar ratio of the lipoic acid and/or the derivative thereof to the inorganic iron salt is (10-200): 1.

The invention further discloses the application of the solvent-free binder and/or the solvent-free binder prepared by the preparation method in a dry environment, a wet environment or an acidic environment.

Wherein, the dry environment refers to an environment with relatively low moisture content, the wet environment refers to an environment with relatively high moisture content, and the acid environment refers to an environment with a tested pH value of less than 7.

According to some embodiments of the present invention, the adhesive of the present invention can bond well to a variety of substrate materials such as skin, plastic, teflon, steel, wood, etc. in an acidic environment with a pH of 1.

Preferably, the application is an application in clinical medicine, such as bonding to a bone defect, a skin wound and the like, and more preferably, the application comprises an application realized by injection.

The preparation method of the solvent-free binder combines lipoic acid or/and derivatives thereof with polyphenol materials through one-step high-temperature self-polymerization and cross-linking of non-covalent bonds (hydrogen bonds) and metal coordination bonds, then inorganic ferric salt such as ferric trichloride and/or ferric sulfate is added into a mixed melt of the lipoic acid or/and the derivatives thereof, and after the melt after the melting and mixing is cooled to room temperature, the initial solid powder material is converted into a viscous state, so that the binder with good universality binding performance and good binding performance in a wet environment is formed.

The preparation method of the invention advances the reaction of the binder, controls the crosslinking degree of the binder through the preparation process, and the obtained binder has groups which can be adhered in dry/wet environment, can be directly applied through injection, and can be immediately used without external stimulation and waiting for reaction.

The adhesive provided by the invention is simple to prepare, does not need too many complex synthetic routes, does not need a long-time reaction process, meanwhile, the used lipoic acid main material belongs to natural biological micromolecules, the safety is high, the biocompatibility is good, the used polyphenol compound has the antibacterial, anti-inflammatory and antioxidant properties, meanwhile, the components endow the adhesive with good photo-thermal conversion performance and adhesive property through metal-polyphenol coordination bonds, the photo-thermal antibacterial property and the stable and efficient adhesion of the adhesive can be realized, meanwhile, the whole system does not contain any solvent, can be used permanently, and can be removed conveniently by using ethanol, and the preparation process is simple, the time consumption is short, no organic synthesis and reagent use are involved, the adhesive can show excellent adhesive performance in dry and wet environments and even acidic environments, and the biocompatibility is good, and the adhesive is particularly suitable for being used as a novel adhesive material in the industrial and medical fields.

The adhesive provided by the invention has good and stable adhesive performance on substrates such as skin, plastics, polytetrafluoroethylene, steel, wood and the like in dry environment, wet environment and acidic (pH is 1) environment.

The adhesive provided by the invention can be used for effectively bonding hard tissues or soft tissues in medical application, and has the potential of being widely applied to focus parts such as clinical bone defects, skin wound healing and the like.

Drawings

Fig. 1 is a diagram showing the process for preparing the solventless adhesive in example 1.

FIG. 2 is a SEM characterization comparison of lipoic acid and the resulting product binder of example 1.

FIG. 3 is a graph comparing the EDS spectra of lipoic acid and the resulting product binder of example 1.

FIG. 4 is an EDS Mapping spectrum of the product binder obtained in example 1.

FIG. 5 is a graph showing the adhesion of the adhesive obtained in example 1 to various substrates.

FIG. 6 is a graph comparing the adhesion of the adhesive obtained in example 1 under different substrates and environments.

FIG. 7 is a graph showing the effect of the sealing property of the underwater adhesive obtained in example 1.

FIG. 8 is a graph showing the photo-thermal antibacterial effect of the adhesive obtained in example 1.

Fig. 9 is a graph showing the biocompatibility test of the adhesive obtained in example 1.

FIG. 10 is a graph showing the adhesion of the adhesive obtained in example 2 to various substrates.

FIG. 11 is a graph showing the adhesion of the adhesive obtained in example 3 to various substrates.

FIG. 12 is a graph showing the adhesion of the adhesive obtained in example 4 to various substrates.

FIG. 13 is a graph showing the adhesion of the adhesive obtained in example 5 to various substrates.

FIG. 14 is a graph showing the adhesion of the adhesive obtained in example 6 to various substrates.

FIG. 15 is a graph showing the adhesion of the adhesive obtained in example 7 to various substrates.

Detailed Description

The present invention is described in detail below with reference to the following embodiments and the attached drawings, but it should be understood that the embodiments and the attached drawings are only used for the illustrative description of the present invention and do not limit the protection scope of the present invention in any way. All reasonable variations and combinations that fall within the spirit of the invention are intended to be within the scope of the invention.

According to the technical scheme of the invention, the specific preparation method of the solvent-free binder comprises the following steps:

(1) melting lipoic acid at 60-200 ℃;

(2) adding polyphenol compounds with the mass of 0.1-20% of the lipoic acid mass into the melt obtained in the step (1) for mixing, and forming a uniform mixed melt at 60-200 ℃;

(3) adding ferric trichloride and/or ferric sulfate into the mixed melt obtained in the step (2) for mixing to form a uniform mixed melt at the temperature of 60-200 ℃;

(4) standing and cooling the mixed melt obtained in the step (3) to room temperature to obtain the binder;

wherein the molar ratio of the lipoic acid to the ferric trichloride and/or the ferric sulfate is (10-200): 1.

Some preferred examples of the above embodiments are further illustrated below:

example 1

The binder is prepared by the following steps:

(1) 1.25g of Lipoic Acid (LA) is added into a glass bottle and heated at 150 ℃ to form a uniform and transparent melt;

(2) under magnetic stirring, adding tannic acid with the mass being 4% of the lipoic acid mass into the melt in the step (1), and reacting at 150 ℃ to form a uniformly mixed melt;

(3) adding ferric trichloride (FeCl) ₃ ) According to n (LA) n (FeCl) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 50:1, and reacting at 150 ℃ to form a uniformly mixed melt;

(4) and (4) standing and cooling the stable melt in the step (3) to room temperature, so that the mixed melt in the step (3) forms a universal binder (LTFe) with adhesive property.

The appearance of the intermediate or final product binder and its cohesiveness produced in the above steps is shown in FIG. 1.

SEM characterization analysis and EDS spectrum scanning are carried out on the raw material lipoic acid LA and the obtained binder LTFe, and the results are respectively shown in the attached figures 2, 3 and 4, and it can be seen that: compared with the initial small flake of the raw material lipoic acid, the surface of the obtained adhesive LTFe is smoother, and Fe and Cl elements are uniformly distributed in the adhesive of the obtained product.

Further, the adhesive properties of the obtained adhesive were verified according to the modified ASTM F2255-05 method for various substrates and in various environments, including pigskin, polyethylene plastic, polytetrafluoroethylene, wood, glass and steel, which were cut in a size of 6cm by 2mm, respectively, and then 100mg ± 5mg of the obtained adhesive was uniformly coated on various substrates having a bonding area of 2cm by 2cm, and photographed after being pressed with a finger for 15 seconds, and the results are shown in fig. 5, in which: the obtained adhesive has better adhesion to different substrates.

The substrate is tested for adhesive property in dry, water and acid solution in the same way, and after being pressed by fingers for 15s, the substrate is tested for lap shear strength on a universal mechanical testing instrument, and the result is shown in figure 6, and can be seen: the obtained adhesive has better adhesion to different substrates in dry/wet and even acid environments, and the lap joint adhesive strength is about 20 kPa.

Further, the obtained adhesive was tested for underwater adhesion sealing effect, including: a10 cm long and 2mm wide mouth was cut at the center of the bottom of a water tank having a length, width and height of 20cm, 10cm and 5cm, respectively, with a knife, and ultrapure water was poured, and the resulting adhesive was injected into the mouth of the bottom of the water tank using a 20ml syringe, and the results were as shown in FIG. 7, from which it can be seen that: after the obtained adhesive is blocked, the water tank bottom does not leak water any more, which shows that the obtained adhesive is not only convenient to use, but also has good underwater blocking and adhesion performance.

Further, the resulting binders were tested for biocompatibility, including: uniformly coating the obtained binders with the mass of 1mg, 2.5mg, 5mg, 7.5mg, 10mg and 15mg on a 1cm by 1cm titanium alloy sheet, putting the sheet into a 24-hole cell culture plate, and carrying out ultraviolet irradiation for 24h for sterilization treatment. The inoculation density per well in a 24-well plate is 10 ⁴ L929 cells of (1), containing 5% CO at 37 ℃ ₂ After the materials are incubated in the incubator for 24 hours, the survival rate of the cells is detected by a CCK8 method, the cell compatibility of the materials is evaluated, and meanwhile, a blank pure titanium alloy sheet is used as a control group. The results are shown in FIG. 8, which shows that: when the mass of the binder is less than or equal to 5mg, the biological safety is good.

Further, the photo-thermal antibacterial effect of the obtained binder is tested, and the test method comprises the following steps: uniformly coating 5mg of adhesive on a 1 cm-1 cm titanium alloy sheet, placing the titanium alloy sheet into 24 holes, and carrying out ultraviolet irradiation for 24h for sterilization treatment. The density of each seed in a 24-well plate is 10 ⁶ CFU of staphylococcus aureus (s. aureus) and escherichia coli (e. coli) using a power density of 1.5W cm ^-1 Irradiating for 5min under 808nm near-infrared laser, placing in an incubator at 37 ℃ for incubation for 24h, sucking 100ul of bacterial culture medium per hole, uniformly coating on a solid agar culture plate, continuously placing the solid agar culture medium coated with the bacterial culture medium in the incubator at 37 ℃ for incubation for 24h, and taking a picture. The results are shown in FIG. 9, where it can be seen that: and through the group of 808nm near-infrared laser irradiation, no colony of any one of staphylococcus aureus (S.aureus) and escherichia coli (E.coli) is formed on the solid culture medium incubated for 24 hours at 37 ℃, which shows that the obtained binder has good photo-thermal property under the irradiation of the near-infrared laser, thereby having good antibacterial performance on the staphylococcus aureus (S.aureus) and the escherichia coli (E.coli).

Example 2

The binder is prepared by the following steps:

(2) under magnetic stirring, adding ellagic acid into the melt in the step (1) according to the mass ratio of 0.4% of lipoic acid, and reacting at 150 ℃ to form a uniformly mixed melt;

(3) ferric trichloride is prepared according to the ratio of n (LA) to n (FeCl) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 100:1, and reacting at 150 ℃ to form a uniformly mixed melt;

(4) and (4) standing the stable melt in the step (3) and cooling to room temperature to enable the mixed melt in the step (3) to form a universal adhesive with adhesive property.

The adhesive property test was carried out in the same manner as in example 1, and the results are shown in FIG. 10, and it can be seen that: the obtained adhesive has better adhesion to different substrates.

Example 3

The binder is prepared by the following steps:

(2) adding epigallocatechin gallate into the melt obtained in the step (1) according to the mass ratio of 0.2% of lipoic acid under magnetic stirring, and reacting at 150 ℃ to form a uniformly mixed melt;

(3) iron trichloride is prepared according to the formula of n (LA) n (FeCl) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 100:1, and reacting at 150 ℃ to form a uniformly mixed melt;

The adhesive property test was carried out in the same manner as in example 1, and the results are shown in FIG. 11, and it can be seen that: the obtained adhesive has better adhesion to different substrates.

Example 4

The binder is prepared by the following steps:

(2) under magnetic stirring, adding procyanidine into the melt in the step (1) according to the mass ratio of 1% of lipoic acid, and reacting at 150 ℃ to form a uniformly mixed melt;

(3) iron trichloride is prepared according to the formula of n (LA) n (FeCl) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 150:1, and reacting at 150 ℃ to form a uniformly mixed melt;

The adhesive property test was carried out in the same manner as in example 1, and the results are shown in FIG. 12, and it can be seen that: the obtained adhesive has better adhesion to different substrates.

Example 5

The binder is prepared by the following steps:

(2) under magnetic stirring, adding gallic acid into the melt in the step (1) according to the mass ratio of 4% of lipoic acid, and reacting at 150 ℃ to form a uniformly mixed melt;

(3) ferric chloride (FeCl) ₃ ) According to n (LA) n (FeCl) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 50:1, and reacting at 150 ℃ to form a uniformly mixed melt;

The adhesion of the obtained adhesive to different substrates was verified, according to the modified ASTM F2255-05 method, different substrates (pigskin, polyethylene, teflon, wood, glass, steel) were cut to a size of 6cm by 2mm, then 100mg ± 5mg of the obtained adhesive was uniformly coated on different substrates having an adhesion area of 2cm by 2cm, and photographed after 15s of finger pressure, and the results are shown in fig. 13, where: the obtained adhesive has better adhesion to different substrates.

Example 6

The binder is prepared by the following steps:

(2) under the magnetic stirring, adding pyro acid into the melt of the step (1) according to the mass ratio of 8 percent of lipoic acid, and reacting at 150 ℃ to form a uniformly mixed melt;

(3) ferric trichloride is prepared according to the ratio of n (LA) to n (FeCl) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 50:1, and reacting at 150 ℃ to form a uniformly mixed melt;

The adhesive property test was carried out in the same manner as in example 1, and the results are shown in FIG. 14, and it can be seen that: the obtained adhesive has better adhesion to different substrates.

Example 7

The binder is prepared by the following steps:

(2) under magnetic stirring, adding tannic acid into the melt in the step (1) according to the mass ratio of lipoic acid of 4%, and reacting at 150 ℃ to form a uniformly mixed melt;

(3) ferric sulfate (Fe) ₂ (SO ₄ ) ₃ ) According to n (LA) n (Fe) ₂ (SO ₄ ) ₃ ) Adding the mixture into the melt obtained in the step (2) at a molar ratio of 100:1, and reacting at 150 ℃ to form a uniformly mixed melt;

The adhesive property test was carried out in the same manner as in example 1, and the results are shown in FIG. 15, and it can be seen that: the obtained adhesive has better adhesion to different substrates.

The above examples are merely preferred embodiments of the present invention, and the scope of the present invention is not limited to the above examples. All technical schemes belonging to the idea of the invention belong to the protection scope of the invention. It should be noted that modifications and embellishments within the scope of the invention may be made by those skilled in the art without departing from the principle of the invention, and such modifications and embellishments should also be considered as within the scope of the invention.

Claims

1. A method of preparing a solventless adhesive comprising:

(1) melting lipoic acid and/or derivatives thereof at 60-200 ℃;

(4) standing and cooling the mixed melt obtained in the step (3) to room temperature to obtain the solvent-free binder;

wherein the polyphenol compound is selected from one or more of tannic acid, ellagic acid, epigallocatechin gallate, procyanidin, gallic acid, pyrogalloc acid; the inorganic ferric salt is selected from ferric trichloride and/or ferric sulfate; the weight of the polyphenol compound is 0.1-20% of the weight of the lipoic acid and/or the derivative thereof, and the molar ratio of the lipoic acid and/or the derivative thereof to the inorganic iron salt is (10-200): 1.

2. The solvent-free binder prepared by the method of claim 1.

3. Use of the solventless adhesive of claim 2 as an adhesive in a dry environment, a wet environment or an acidic environment.

4. Use of the solventless adhesive of claim 2 in the preparation of an adhesive for clinical medicine.