A bioadhesive and its preparation method and application

Abstract

The present invention relates to a bioadhesive and a preparation method and application thereof, which contains the following components: polyacrylate, N-hydroxysuccinimide, chitosan, acetic acid and water. The preparation method comprises the following steps: weighing acrylic acid and N-hydroxysuccinimide, adding deionized water and mixing evenly to obtain solution A; weighing chitosan, dissolving it in acetic acid solution, mixing evenly to obtain solution B; at room temperature, mixing the solution A and the solution B evenly, curing under ultraviolet light, and obtaining an adhesive sample. The present invention can be used to prepare medical adhesive materials.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a bioadhesive and a preparation method and application thereof. Background Art

[0002] According to statistical reports, there are about 114 million cases of trauma each year worldwide, of which 36 million are in the United States alone. These traumas include skin wounds, but also any surgical or traumatic damage to solid and hollow organs, connective tissue, muscles, tendons, and membranes. Rapid hemostasis and wound closure after trauma are not only the core technologies of basic operations during surgical procedures, but also problems that must be faced in surgical operations. These problems not only threaten life safety, but also bring a large economic burden. Suturing is the most commonly used method to achieve tissue wound healing, but traditional suturing methods often have disadvantages such as time-consuming, requiring anesthesia, and forming scar tissue. In addition, suturing methods cannot stop bleeding quickly, so traditional suturing methods are not the best methods for wound closure and hemostasis.

[0003] The concept of modern medicine is to minimize the pain of patients, to make the patients recover as quickly as possible, and to restore the physiological function of damaged tissues to the greatest extent possible, and to restore the appearance of the wound to a perfect state. Bioadhesives are widely used as a perfect substitute for traditional suturing methods because of their quick and simple operation, ability to achieve non-invasive closure, no damage to the tissues around the injured part, reduced pain during suturing, no need for secondary surgery to remove the adhesive, ability to avoid leakage of body fluids and air, no scar formation at the adhesive site, and being used as a carrier for the release of drugs and factors in the local area of ​​the wound. Therefore, in the past few decades, a variety of bioadhesives have been developed to provide more reliable, more practical and faster methods of tissue closure and hemostasis without damaging tissue vascularization and avoiding the risk of leakage.

[0004] Bioadhesives, also known as medical adhesives, are a type of material used in tissue engineering. They have good wetting and bonding properties, and can bond tissues together through various physical or chemical effects, achieving wound closure and sealing effects. Depending on the location of the tissue and the field of application, bioadhesives with corresponding functions can be selected, so they have received extensive attention and research from scientific researchers, providing a powerful technical means for hemostasis in surgical operations, preventing the leakage of body fluids and air, and bonding soft or hard tissues.

[0005] However, currently commercially available tissue adhesives provide only weak or slow adhesion to blood-covered tissue surfaces and cannot achieve rapid and effective hemostasis, which greatly limits their utility in clinical applications.

[0006] The Chinese invention patent application with publication number CN104922726A discloses a degradable soft tissue adhesive and a preparation method thereof. The adhesive is composed of the following components in parts by mass: 34-52 parts of n-butyl α-cyanoacrylate, 4-13 parts of chitosan, 5-19 parts of vinyl pyrrolidone, 2-9 parts of benzoyl peroxide, 15-26 parts of pentaerythritol, 2-8 parts of hydroxyethyl cellulose, 7-15 parts of glycerol, 5-13 parts of polyacrylate, and 4-11 parts of methacrylate.

[0007] The tissue hemostatic adhesion performance of the above adhesive is still insufficient, and there are too many components and the preparation process is complicated. Summary of the invention

[0008] The present invention aims to solve the technical problem of insufficient hemostatic adhesion of bioadhesives in the prior art, and provides a polyacrylate / chitosan composite bioadhesive and its preparation method and application. It can achieve wound hemostasis and sealing. Since polyacrylate has good adhesion and chitosan is a natural polysaccharide, the composite of the two has good tissue adhesion, excellent hemostatic effect, and low biological toxicity.

[0009] To this end, the present invention provides a bioadhesive containing the following components in a mass volume ratio: 15% to 30% w / v polyacrylate, 1% to 4% w / v N-hydroxysuccinimide, 1% to 4% w / v chitosan, 0.8 to 1% w / v acetic acid, and the remainder being water.

[0010] Preferably, the mass volume ratio of the components is: 30% w / v polyacrylate, 4% w / v N-hydroxysuccinimide, 4% w / v chitosan, 1% w / v acetic acid, and the balance is water.

[0011] The present invention also provides a method for preparing a bioadhesive, which comprises the following steps: (1) weighing acrylic acid and N-hydroxysuccinimide, adding deionized water and mixing evenly to obtain a solution A; (2) weighing chitosan, dissolving the chitosan in an acetic acid solution, and mixing evenly to obtain a solution B; (3) at room temperature, mixing the solution A and the solution B evenly, and curing them under ultraviolet light to obtain an adhesive sample.

[0012] Preferably, in step (3), the wavelength of the ultraviolet light is 365 nm.

[0013] The invention also provides an application of a bioadhesive in preparing a medical adhesive material.

[0014] The present invention has the following beneficial effects:

[0015] (1) The polyacrylate in the present invention has good adhesion and can have a good adhesion effect on various tissues;

[0016] (2) After N-hydroxysuccinimide reacts with acrylic acid, it can undergo covalent cross-linking with the amine groups on the tissue surface, further enhancing tissue adhesion;

[0017] (3) Chitosan can adsorb red blood cells and platelets and has a good hemostatic effect;

[0018] (4) Polyacrylate also has certain antibacterial properties, which can reduce the risk of bacterial contamination during the use of adhesives;

[0019] (5) Bioadhesives are stored in the form of gel, which makes them easy to carry and use;

[0020] (6) Polyacrylate / chitosan composite bioadhesive has good biocompatibility and low biotoxicity;

[0021] (7) The raw materials of the bioadhesive prepared by the present invention include acrylic acid, N-hydroxysuccinimide, acetic acid and chitosan, and the raw materials are easily available and low in cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Schematic diagram of the pigskin shear adhesion strength performance test experiment;

[0023] Figure 2 Results of shear bond strength of bioadhesives with different polyacrylate contents to pig skin;

[0024] Figure 3 Schematic diagram of hemostatic adhesion of the bioadhesive of the present invention to rat liver;

[0025] Figure 4 Schematic diagram of hemostatic adhesion of the bioadhesive of the present invention to a rat heart. DETAILED DESCRIPTION

[0026] The present invention provides a method for preparing a polyacrylate / chitosan composite bioadhesive and its application. Those skilled in the art can refer to the contents of this article and make appropriate improvements to the relevant process parameters to achieve the desired effect.

[0027] The raw materials used in the present invention are all common commercial products and can be purchased in the market.

[0028] The present invention will be further described below in conjunction with embodiments.

[0029] Example 1

[0030] The preparation method is as follows:

[0031] (1) Weighing a certain amount of acrylic acid and N-hydroxysuccinimide, adding deionized water and mixing evenly to obtain solution A;

[0032] (2) Then weigh a certain amount of chitosan, dissolve it in the solution, and mix it evenly to obtain solution B;

[0033] (3) At room temperature, solutions A and B were mixed evenly and cured under ultraviolet light of 365 nm to obtain an adhesive sample.

[0034] The bioadhesive prepared by the above method was named PANS15, and the mass volume ratio of each component in the sample was: 15% w / v polyacrylate, 1% w / v N-hydroxysuccinimide, 1% w / v chitosan, 0.8 w / v acetic acid, and the balance was water.

[0035] Example 2

[0036] A bioadhesive was prepared and named PANS20, wherein the weight volume ratio of each component in the sample was: 20% w / v polyacrylate, 2% w / v N-hydroxysuccinimide, 2% w / v chitosan, 0.9 w / v acetic acid, and the balance was water. The rest was the same as in Example 1.

[0037] Example 3

[0038] A bioadhesive was prepared and named PANS25, wherein the weight volume ratio of each component in the sample was: 25% w / v polyacrylate, 3% w / v N-hydroxysuccinimide, 3% w / v chitosan, 1 w / v acetic acid, and the balance was water. The rest was the same as in Example 1.

[0039] Example 4

[0040] A bioadhesive was prepared and named PANS30, wherein the weight volume ratio of each component in the sample was: 30% w / v polyacrylate, 4% w / v N-hydroxysuccinimide, 4% w / v chitosan, 1 w / v acetic acid, and the balance was water. The rest was the same as in Example 1.

[0041] Example 5

[0042] The bioadhesive prepared by the present invention, also known as a medical adhesive, can be used in surgery, such as hemostasis, sealing and closure of liver, heart and other tissues, and can replace traditional surgical methods such as sutures, staples and the like.

[0043] Example 6 is a test experiment of shear bonding strength of bioadhesives with different polyacrylate contents

[0044] After removing the grease from the surface of the pigskin, the pigskin was cut into strips with a length and width of 50 mm*25 mm, and the bioadhesive prepared in Examples 1-4 was prepared into a shape of 25 mm*25 mm*1 mm. The two were bonded and fixed, and the shear bonding strength was measured using a universal mechanical testing machine. The test diagram is shown in FIG. Figure 1 The test results are shown in Figure 2shown.

[0045] Depend on Figure 2 The results of the bonding strength test show that the bonding strength of different carboxymethyl chitosan bioadhesives is different. Among them, PANS30 is significantly stronger than PANS15 (* represents statistical difference, p<0.01).

[0046] Example 7 is a hemostatic adhesion test of the bioadhesive of the present invention on rat liver

[0047] Experimental method: Use surgical scissors to cut a 2cm*0.5cm wound on the rat, bleed for 10 seconds, then use materials to stop bleeding, and observe the hemostatic effect. If there is no more blood oozing, it means that the hemostasis is successful.

[0048] Example 8 is a hemostatic adhesion test of the bioadhesive of the present invention on rat heart

[0049] Experimental method: Use a needle with an outer diameter of 1.2mm to make a wound on the rat's heart. After bleeding for 3 seconds, use materials to stop bleeding and observe the hemostatic effect. If there is no more blood oozing, it means that the hemostasis is successful.

[0050] However, what is described above is only a specific embodiment of the present invention and should not be used to limit the scope of implementation of the present invention. Therefore, the replacement of equivalent components, or equivalent changes and modifications made according to the scope of protection of the present invention should still fall within the scope covered by the claims of the present invention.

Claims

1. A use of a bioadhesive in the preparation of a medical adhesive material, characterized in that: The invention comprises the following components in a mass volume ratio: 30% w / v polyacrylate, 4% w / v N-hydroxysuccinimide, 4% w / v chitosan, 1% w / v acetic acid, and the balance is water; The preparation method of the bioadhesive comprises the following steps: (1) Weighing acrylic acid and N-hydroxysuccinimide, adding deionized water and mixing well to obtain solution A; (2) weighing chitosan, dissolving it in acetic acid solution, and mixing well to obtain solution B; (3) At room temperature, the solution A and the solution B are mixed evenly, and cured under ultraviolet light with a wavelength of 365 nm to obtain an adhesive sample.

Images