Preparation method of Chinese herbal medicine anticoagulant antibacterial composite coating

Abstract

The invention discloses a preparation method of a Chinese herbal medicine anticoagulant antibacterial composite coating, which comprises the following steps: firstly, carrying out adhesion bottom layer modification on a bionic polydopamine material based on a mussel viscous protein structure, and forming a layer of large-network polymer structure on a polydopamine adhesion coating through Michael reaction and Schiff base reaction; further, nanofibers are formed on the surface through an electrostatic spinning technology to load traditional Chinese medicine active ingredients; secondly, preparing an anticoagulant coating on the basis of the polydopamine-astragalus polysaccharide phosphate composite material; and finally, preparing the antibacterial coating based on the prepared berberine-silk fibroin solution. The invention provides a new path for solving the problems of poor anticoagulation effect, limited antibacterial effect and the like of the current biological coating by using the Chinese herbal medicine active ingredients and the biological material, the anticoagulation function and the antibacterial effect are obviously improved, the side effect is small, the slow release of the medicine can be realized, and the service life of medical equipment is prolonged.

Description

Technical Field

[0001] The present invention relates to the field of Chinese herbal medicine composite coatings, and more specifically to a method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating. Background Art

[0002] The surface coating of Chinese patent medicine mainly plays the following roles:

[0003] 1. Protect drugs: The surface coating can effectively isolate harmful substances such as moisture, oxygen and microorganisms in the air, prevent drugs from getting damp, oxidized and deteriorating, thereby extending the shelf life of drugs.

[0004] 2. Improve drug efficacy: Some coating materials have a sustained-release effect, which can slowly release drugs in the body and maintain long-lasting and stable drug efficacy. In addition, some coatings can also improve the bioavailability of drugs, making them easier to be absorbed by the human body.

[0005] 3. Enhanced user experience: Surface coating can improve the taste of the drug, reduce the irritation and side effects of the drug, and improve the patient's comfort in taking the drug.

[0006] Currently, biological coatings have the following shortcomings: single function, poor anticoagulant effect, poor antibacterial effect, uneven application, etc. Summary of the invention

[0007] In order to overcome the above-mentioned defects of the prior art, the present invention provides a method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating.

[0008] The technical solution of the present invention is as follows:

[0009] A method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating comprises the following steps:

[0010] Firstly, the adhesive bottom layer is modified by polydopamine material based on the bionic structure of mussel adhesive protein, and a large network polymer structure is formed on the polydopamine adhesive coating through Michael reaction and Schiff base reaction. Then, nanofibers are formed on its surface through electrospinning technology to load the active ingredients of traditional Chinese medicine, thereby constructing a traditional Chinese medicine coating on the surface of medical devices and forming a traditional Chinese medicine controlled release system, which effectively controls the release rate and pattern of the active ingredients of traditional Chinese medicine and maintains its biological activity.

[0011] Secondly, the anticoagulant coating was prepared based on the polydopamine-astragalus polysaccharide phosphate composite material;

[0012] Finally, the antibacterial coating was prepared based on the prepared berberine-silk fibroin solution.

[0013] Specifically include:

[0014] ① Construction of the adhesion base

[0015] [Step 1] Pre-treat the substrate material: prepare 100 mL of a 2 wt% dopamine hydrochloride aqueous solution with a pH of 8.5, immerse the pre-treated substrate material in an alkaline solution containing dopamine, and form a polydopamine coating on the surface of the material by utilizing the self-polymerization reaction of dopamine under alkaline conditions. Stir at room temperature for 36 hours, take it out, rinse it with ultrapure water, vacuum dry it, and load a layer of polydopamine bottom layer on its surface.

[0016] [Step 2] Covalent bonding is performed on the surface of a substrate containing amine or thiol groups through Michael addition and Schiff base reaction, the polydopamine-coated substrate is immersed in a solution containing a polymer precursor, and a polymer network is formed through a chemical cross-linking reaction.

[0017] [Step 3] Use electrospinning technology to load the active ingredients of traditional Chinese medicine, and mix the traditional Chinese medicine extract with the polymer based on electrostatic force to form nanofibers.

[0018] ② Construction of anticoagulant coating

[0019]

Step 1

[0020] Perform preliminary sterilization and disinfection on the blood-contact medical devices to be assembled, rinse them with medical disinfectant, put them in a ventilated place to air-dry, and then sterilize them with ethylene oxide, and store them in a stainless steel box at room temperature and pressure for standby use;

[0021]

Step 2

[0022] First, the astragalus polysaccharide after alkali extraction, alcohol precipitation and purification is dehydrated and dried. Secondly, according to the ratio of concentrated sulfuric acid to astragalus polysaccharide of 6:1, astragalus polysaccharide is quickly added to concentrated sulfuric acid, and after stirring and reacting at 0°C for 4 hours, the pH of the reaction system is adjusted to weak alkalinity to obtain astragalus polysaccharide sulfate solution; finally, the obtained solution is dialyzed for 20 hours, poured into 2 times the volume of 95% ethanol, and precipitated; after standing, the precipitate is filtered out and dried to obtain astragalus polysaccharide sulfate;

[0023]

Step 3

[0024] First, polysaccharide sulfate or collagen is dissolved in deionized water, a certain amount of sodium nitrite is added, and the mixture is stirred in an ice bath under acidic conditions for 2 hours; the pH of the solution is adjusted to neutral, and then dialyzed for 24 hours, during which the deionized water is replaced 3 times to obtain a polysaccharide sulfate coating solution and a collagen coating solution.

[0025] Secondly, add appropriate amounts of sodium chloride and sodium cyanoborohydride to the obtained polysaccharide sulfate coating liquid and collagen coating liquid, mix them thoroughly, and adjust the solution pH to 3.5; immerse the blood-contact medical device material in the polysaccharide sulfate coating liquid, shake and react in a constant temperature water bath at 40°C for 2 hours, take it out and wash the polysaccharide sulfate that is not firmly bound to the surface with deionized water, and blow it dry with nitrogen. The dried blood-contact medical device material is immediately immersed in the collagen coating liquid, shake and react in a constant temperature water bath at 40°C for 2 hours, take it out and wash the collagen that is not firmly bound to the surface with deionized water, and blow it dry with nitrogen. Repeat the above process 4 times, and after drying, obtain the target blood-contact medical device with a composite anticoagulant coating of astragalus polysaccharide phosphate coating.

[0026] ③Construction of antibacterial coating

[0027] [Step 1] Weigh the berberine powder extracted in 3.3.2 and dissolve it in deionized water. The concentration of the berberine solution is 4 mg / mL;

[0028] [Step 2] Dilute the silk fibroin solution with deionized water to a concentration of 7% (w / v), add glycerol to the silk fibroin solution, the mass proportion of glycerol is 30%, and mix well;

[0029] [Step 3] Evenly mix 4 mg / mL berberine solution and silk fibroin glycerol mixed solution, where the mass ratio of silk fibroin to berberine is 10:1.

[0030] [Step 4] Place the blood-contact medical device after the first two treatments into the prepared antibacterial coating solution, and construct the antibacterial coating using the dip coating method.

[0031] Technical effects and advantages of the present invention:

[0032] Compared with existing technologies, an innovative new path of "active ingredients of Chinese herbal medicine + biomaterials" is proposed to solve the problems of poor anticoagulant effect and limited antibacterial effect of current biological coatings. It significantly improves the anticoagulant function and antibacterial effect, has few side effects, can achieve sustained release of drugs, and extend the service life of medical devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 It is a schematic diagram of the overall structure of the present invention. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] ① Construction of the adhesion base

[0036] [Step 1] Pre-treat the substrate material: prepare 100 mL of a 2 wt% dopamine hydrochloride aqueous solution with a pH of 8.5, immerse the pre-treated substrate material in an alkaline solution containing dopamine, and form a polydopamine coating on the surface of the material by utilizing the self-polymerization reaction of dopamine under alkaline conditions. Stir at room temperature for 36 hours, take it out, rinse it with ultrapure water, vacuum dry it, and load a layer of polydopamine bottom layer on its surface.

[0037] [Step 2] Covalent bonding is performed on the surface of a substrate containing amine or thiol groups through Michael addition and Schiff base reaction, the polydopamine-coated substrate is immersed in a solution containing a polymer precursor, and a polymer network is formed through a chemical cross-linking reaction.

[0038] [Step 3] Use electrospinning technology to load the active ingredients of traditional Chinese medicine, and mix the traditional Chinese medicine extract with the polymer based on electrostatic force to form nanofibers.

[0039] ② Construction of anticoagulant coating

[0040]

Step 1

[0041] Perform preliminary sterilization and disinfection on the blood-contact medical devices to be assembled, rinse them with medical disinfectant, put them in a ventilated place to air-dry, and then sterilize them with ethylene oxide, and store them in a stainless steel box at room temperature and pressure for standby use;

[0042]

Step 2

[0043] First, the astragalus polysaccharide after alkali extraction, alcohol precipitation and purification is dehydrated and dried. Secondly, according to the ratio of concentrated sulfuric acid to astragalus polysaccharide of 6:1, astragalus polysaccharide is quickly added to concentrated sulfuric acid, and after stirring and reacting at 0°C for 4 hours, the pH of the reaction system is adjusted to weak alkalinity to obtain astragalus polysaccharide sulfate solution; finally, the obtained solution is dialyzed for 20 hours, poured into 2 times the volume of 95% ethanol, and precipitated; after standing, the precipitate is filtered out and dried to obtain astragalus polysaccharide sulfate;

[0044]

Step 3

[0045] First, polysaccharide sulfate or collagen is dissolved in deionized water, a certain amount of sodium nitrite is added, and the mixture is stirred in an ice bath under acidic conditions for 2 hours; the pH of the solution is adjusted to neutral, and then dialyzed for 24 hours, during which the deionized water is replaced 3 times to obtain a polysaccharide sulfate coating solution and a collagen coating solution.

[0046] Secondly, add appropriate amounts of sodium chloride and sodium cyanoborohydride to the obtained polysaccharide sulfate coating liquid and collagen coating liquid, mix them thoroughly, and adjust the solution pH to 3.5; immerse the blood-contact medical device material in the polysaccharide sulfate coating liquid, shake and react in a constant temperature water bath at 40°C for 2 hours, take it out and wash the polysaccharide sulfate that is not firmly bound to the surface with deionized water, and blow it dry with nitrogen. The dried blood-contact medical device material is immediately immersed in the collagen coating liquid, shake and react in a constant temperature water bath at 40°C for 2 hours, take it out and wash the collagen that is not firmly bound to the surface with deionized water, and blow it dry with nitrogen. Repeat the above process 4 times, and after drying, obtain the target blood-contact medical device with a composite anticoagulant coating of astragalus polysaccharide phosphate coating.

[0047] ③Construction of antibacterial coating

[0048] [Step 1] Weigh the berberine powder extracted in 3.3.2 and dissolve it in deionized water. The concentration of the berberine solution is 4 mg / mL;

[0049] [Step 2] Dilute the silk fibroin solution with deionized water to a concentration of 7% (w / v), add glycerol to the silk fibroin solution, the mass proportion of glycerol is 30%, and mix well;

[0050] [Step 3] Evenly mix 4 mg / mL berberine solution and silk fibroin glycerol mixed solution, where the mass ratio of silk fibroin to berberine is 10:1.

[0051] [Step 4] Place the blood-contact medical device after the first two treatments into the prepared antibacterial coating solution, and construct the antibacterial coating using the dip coating method.

[0052] If the solution is not complicated and point 4 has been explained in great detail, especially for invention patents, point 7 can be omitted.

[0053] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating, characterized in that: The following steps are involved: Firstly, the adhesive bottom layer is modified by polydopamine material based on the bionic structure of mussel adhesive protein, and a large network polymer structure is formed on the polydopamine adhesive coating through Michael reaction and Schiff base reaction. Then, nanofibers are formed on its surface through electrospinning technology to load the active ingredients of traditional Chinese medicine, thereby constructing a traditional Chinese medicine coating on the surface of medical devices and forming a traditional Chinese medicine controlled release system, which effectively controls the release rate and pattern of the active ingredients of traditional Chinese medicine and maintains its biological activity. Secondly, the anticoagulant coating was prepared based on the polydopamine-astragalus polysaccharide phosphate composite material; Finally, the antibacterial coating was prepared based on the prepared berberine-silk fibroin solution.

2. The method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating according to claim 1, characterized in that: The construction of the adhesion base layer includes: [Step 1] Pre-treat the substrate material: prepare 100 mL of a 2 wt% dopamine hydrochloride aqueous solution with a pH of 8.5, immerse the pre-treated substrate material in an alkaline solution containing dopamine, and form a polydopamine coating on the surface of the material by utilizing the self-polymerization reaction of dopamine under alkaline conditions; stir at room temperature for 36 hours, take it out, rinse it with ultrapure water, vacuum dry it, and load a layer of polydopamine bottom layer on its surface; [Step 2] Covalently bonding on the surface of a substrate containing amine or thiol groups through Michael addition and Schiff base reaction, immersing the polydopamine-coated substrate in a solution containing a polymer precursor, and forming a polymer network through a chemical cross-linking reaction; [Step 3] Use electrospinning technology to load the active ingredients of traditional Chinese medicine, and mix the traditional Chinese medicine extract with the polymer based on electrostatic force to form nanofibers.

3. The method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating according to claim 1, characterized in that: Construction of anticoagulation coating, including: 【Step 1】Pretreatment of medical devices / materials Perform preliminary sterilization and disinfection on the blood-contact medical devices to be assembled, rinse them with medical disinfectant, put them in a ventilated place to air-dry, and then sterilize them with ethylene oxide, and store them in a stainless steel box at room temperature and pressure for standby use; 【Step 2】Sulfation treatment of astragalus polysaccharide First, the astragalus polysaccharide after alkali extraction, alcohol precipitation and purification is dehydrated and dried; secondly, according to the ratio of concentrated sulfuric acid to astragalus polysaccharide substance of 6:1, astragalus polysaccharide is quickly added to concentrated sulfuric acid, and after stirring and reacting at 0°C for 4 hours, the pH of the reaction system is adjusted to weak alkalinity to obtain an astragalus polysaccharide sulfate solution; finally, the obtained solution is dialyzed for 20 hours, poured into 2 times the volume of 95% ethanol, and precipitated; after standing, the precipitate is filtered out and dried to obtain astragalus polysaccharide sulfate; 【Step 3】Preparation of coating First, polysaccharide sulfate or collagen is dissolved in deionized water, a certain amount of sodium nitrite is added, and the mixture is stirred in an ice bath under acidic conditions for 2 hours; the pH of the solution is adjusted to neutral, and then dialyzed for 24 hours, during which the deionized water is replaced 3 times, to obtain a polysaccharide sulfate coating solution and a collagen coating solution; Secondly, add appropriate amounts of sodium chloride and sodium cyanoborohydride to the obtained polysaccharide sulfate coating liquid and collagen coating liquid respectively, mix them thoroughly, and adjust the pH of the solution to 3.5; immerse the blood-contact medical device material in the polysaccharide sulfate coating liquid, shake and react in a constant temperature water bath at 40°C for 2 hours, take out and wash the polysaccharide sulfate that is not firmly bound to the surface with deionized water, and blow dry with nitrogen; the dried blood-contact medical device material is immediately immersed in the collagen coating liquid, shake and react in a constant temperature water bath at 40°C for 2 hours, take out and wash the collagen that is not firmly bound to the surface with deionized water, and blow dry with nitrogen; repeat the above process 4 times, and after drying, obtain the target blood-contact medical device with a composite anticoagulant coating of astragalus polysaccharide phosphate coating.

4. The method for preparing a Chinese herbal medicine anticoagulant and antibacterial composite coating according to claim 1, characterized in that: Construction of antimicrobial coating, including: [Step 1] Weigh the berberine powder extracted in 3.3.2 and dissolve it in deionized water. The concentration of the berberine solution is 4 mg / mL; [Step 2] Dilute the silk fibroin solution with deionized water to a concentration of 7% (w / v), add glycerol to the silk fibroin solution, the mass proportion of glycerol is 30%, and mix well; [Step 3] Evenly mix the 4 mg / mL berberine solution and the silk fibroin glycerol mixed solution, wherein the mass ratio of silk fibroin to berberine is 10:1; [Step 4] Place the blood-contact medical device after the first two treatments into the prepared antibacterial coating solution, and construct the antibacterial coating using the dip coating method.

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