CN114573015B - Nanometer zinc oxide composite antibacterial agent dispersion liquid and preparation method thereof - Google Patents

Abstract

The invention discloses a nano zinc oxide antibacterial agent and a preparation method thereof, which belongs to the technical field of nano powder. The invention adopts a direct precipitation method to prepare nano zinc oxide with a particle size of less than 50 nm. The zinc source is added to the sodium hydroxide solution to directly precipitate to obtain nano-zinc oxide. However, too fast reaction will affect the morphology controllability, so the present invention adds a certain amount of urea to regulate it; in addition, adding a complexing agent, different preparations can be made. For nanometer zinc oxide with a particle size, trisodium citrate is preferably used as the complexing agent. By nanonizing Chinese herbal medicine and compounding it with nano-zinc oxide, a nano-zinc oxide composite antibacterial agent is prepared. Nano-zinc oxide and nano-Chinese herbal medicine are combined through polycarboxylic acid, and then nano-zinc oxide and nano-Chinese herbal medicine are loaded through an inorganic layered silicate dispersant to form a composite antibacterial agent. Through nano-homogenization technology, a nano-zinc oxide composite antibacterial agent dispersion with small particle size, uniform particle size distribution, and low stability is prepared.

Description

A kind of nano zinc oxide composite antibacterial agent dispersion liquid and preparation method thereof

Technical field

The invention relates to the technical field of nanopowders, and in particular to a nanometer zinc oxide antibacterial agent and a preparation method thereof.

Background technique

Among many nanomaterial antibacterial agents, nano-zinc oxide has a strong inhibitory or killing effect on pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, and Salmonella. As a new zinc source, nano-zinc oxide has It not only has selective toxicity and good biocompatibility, but also has high biological activity, good immune regulation ability and high absorption rate. Therefore, it has attracted more and more attention from relevant researchers. Its antibacterial mechanism mainly lies in the release of free Zn ²⁺ , the interaction between nanoparticles and bacterial cells, and the generation of ROS active oxygen radicals. In addition, nano-zinc oxide particles have photocatalytic properties and can Produces optical toxicity and has a lethal effect on bacteria. However, the use of nano-zinc oxide increases the chance of zinc oxide being exposed to the body, and it inevitably enters the environment and living organisms, causing harm to human health and ecosystem safety. Therefore, the biological safety and ecological safety of nano-zinc oxide Toxicological issues have attracted widespread attention (Journal of Biomedical Nanotechnology, 2021, 17, 2420–2432). Therefore, reducing the dosage of nano-zinc oxide and improving the effect of nano-zinc oxide has become a research hotspot.

Chinese herbal medicines have good antibacterial effects. Antibacterial Chinese herbal medicines can inhibit the growth and reproduction of pathogenic microorganisms, improve the body's resistance, and are used to treat infectious diseases. Antibacterial Chinese herbal medicines contain active ingredients such as alkaloids, flavonoids and coumarin, which can inhibit and kill a variety of pathogenic microorganisms. Chinese herbal medicines with broad-spectrum antibacterial properties include honeysuckle, forsythia, Daqingye, isatis root, indigo naturalis, coptis, cork, skullcap, horsetail, purpurea, dandelion and so on. For example, the main component of Coptis chinensis and Cortex Phellodendron is berberine (berberine), which has broad-spectrum antibacterial effects against a variety of Gram-negative bacteria and positive bacteria such as Shigella dysenteriae, Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus, etc. Has an inhibitory effect. It is often used for diseases such as enteritis, pneumonia, hematuria, sores and swelling. At present, there have been studies using Chinese herbal medicine extracts as antibacterial preparations, which have achieved good results.

Nano-Chinese herbal medicine is the application of nanotechnology to the field of Chinese herbal medicine. After the Chinese medicine is made into nanoparticles, the particles of the drug become very small, which increases the contact area with the solvent, which can improve the dissolution rate and amount of its ingredients. The cell walls of conventional Chinese medicines are generally not destroyed, and many active ingredients in cells cannot penetrate the cell wall and cannot be extracted and utilized. If the traditional Chinese medicine is nanosized, all the cells will be broken, and almost all the components in the cells can be extracted and utilized or taken directly and absorbed by the human body. The bioavailability of poorly soluble drugs such as mineral drugs can be improved by being made into nanoparticles.

If nano zinc oxide and nano Chinese herbal medicine are used in combination, the antibacterial properties of both can be fully utilized and the biological risks of nano zinc oxide can be reduced. Therefore, it is particularly important to develop a preparation process for mixing the two. To modify organic matter on the surface of inorganic nanoparticles, a commonly used method is surface modification, including physical modification and chemical modification. At present, physical modification is the most commonly used, but it is combined through non-covalent bonds, the charge transfer efficiency between the two is low, and the synergistic effect is not obvious.

Contents of the invention

In view of the existing deficiencies, the present invention is proposed in order to provide a preparation method of nano-zinc oxide antibacterial agent with controllable morphology and particle size, and at the same time obtain a nano-zinc oxide composite antibacterial agent dispersion with extremely high dispersion. technical solutions.

One of the purposes of the present invention is to provide a method for preparing a nano zinc oxide antibacterial agent with controllable morphology and particle size, which includes the following steps:

Add the zinc source to the mixed solution of sodium hydroxide and urea, add the complexing agent, and react at 40-90°C.

Further, the molar ratio of sodium hydroxide and urea in the mixed solution of sodium hydroxide and urea is 0.032: (0.00~0.04), in which the number of moles of urea is not 0.

Further, the molar ratio of sodium hydroxide to the zinc source in the mixed solution of sodium hydroxide and urea is 4:1.

Further, the complexing agent includes one of disodium citrate, trisodium citrate, sodium malate or sodium tartrate, and the molar amount is 5%-50% of the zinc source.

The second object of the present invention is to provide nano zinc oxide prepared by the preparation method.

The third object of the present invention is to provide a method for preparing a nano zinc oxide composite antibacterial agent dispersion prepared from the nano zinc oxide antibacterial agent, including the following steps:

Add water-soluble polycarboxylic acid to water to dissolve, divide it into 2 parts of equal volume, add the nano-zinc oxide to one part, add an equal mass of nano-Chinese herbal medicine powder, and at the same time add 1-(3-dimethylaminopropyl base)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to obtain a first solution; in addition, the inorganic layered silicate dispersant was added to another portion , homogeneous, until all the inorganic layered silicate dispersants are fully contacted with water to form a transparent colloid, and a second solution is obtained; finally, the first solution and the second solution are mixed and homogenized; the water-soluble polycarboxylic acid Acid accounts for 5-50wt%, nano zinc oxide antibacterial agent accounts for 0.5-5wt%, EDC and NHS account for 0.5-5wt%, inorganic layered silicate dispersant accounts for 0-10wt%, and the balance is water , the total amount is 100wt%.

Further, the Chinese herbal medicine is one or more of dandelion, honeysuckle, coptis, phellodendron, skullcap or forsythia.

Further, the preparation method of the nano-Chinese herbal medicine powder is: put equal masses of Chinese herbal medicine powder and soluble starch or soluble maltodextrin into a cell-grade ultrafine grinder, and grind at low temperature for 2-10 minutes.

The invention discloses the following technical effects:

1. The present invention prepares nano zinc oxide with a particle size below 50 nm by using a direct precipitation method. The key technology is: adding zinc source to sodium hydroxide solution can directly precipitate to obtain nano-zinc oxide, but too fast reaction will affect the morphology controllability, so the present invention adds a certain amount of urea to regulate it; in addition, adding complex mixture to prepare nano zinc oxide with different particle sizes, preferably trisodium citrate as the complexing agent.

2. The present invention prepares a nano zinc oxide composite antibacterial agent by nanonizing Chinese herbal medicine and compounding it with nano zinc oxide. The key technology is to combine nano zinc oxide and nano Chinese herbal medicine through polycarboxylic acid, and then load nano zinc oxide and nano Chinese herbal medicine through an inorganic layered silicate dispersant to form a composite antibacterial agent.

3. The present invention uses nano-homogenization technology to prepare nano-zinc oxide composite antibacterial agent dispersion with small particle size, uniform particle size distribution and good stability.

Detailed ways

Various exemplary embodiments of the invention will now be described in detail. This detailed description should not be construed as limitations of the invention, but rather as a more detailed description of certain aspects, features and embodiments of the invention.

It should be understood that the terms used in the present invention are only used to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges in the present invention, it should be understood that every intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or value intermediate within a stated range and any other stated value or value intermediate within a stated range is also included within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded from the range.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only the preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and/or materials in connection with which the documents relate. In the event of conflict with any incorporated document, the contents of this specification shall prevail.

It will be apparent to those skilled in the art that various modifications and changes can be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to the skilled person from the description of the invention. The specification and examples of the present invention are exemplary only.

The words "includes", "includes", "has", "contains", etc. used in this article are all open terms, which mean including but not limited to.

Example 1

Add 0.008 mol zinc sulfate heptahydrate to a mixed solution of 0.032 mol sodium hydroxide and 0.04 mol urea, add 0.004 mol trisodium citrate, and 40 g deionized water, and react at 40°C for 1 hour. After the reaction is complete, wash several times with clean water. , and then dried to obtain nano zinc oxide.

Put dandelion, coptis and soluble starch into a cell-level ultrafine grinder (the total mass of dandelion and coptis is equal to the mass of soluble starch), and grind at -10°C for 5 minutes to prepare nano-sized Chinese herbal medicine powder.

Add 5% water-soluble polycarboxylic acid to water to dissolve, and divide into 2 parts of equal volume. Add nano-zinc oxide with a mass ratio of 0.5% to one of the portions, add equal mass of nano-Chinese herbal medicine powder, and simultaneously add 0.5% EDC and 0.5% NHS to obtain the first solution; add 10% inorganic layered silicate The dispersant is added to another portion and homogenized until all the inorganic layered silicate dispersants are fully contacted with water to completely form a transparent colloid to obtain a second solution; finally, the first solution and the second solution are mixed and homogenized. quality. Preparation of nano-zinc oxide composite antibacterial agent dispersion.

The 1-minute antibacterial rate of the nano zinc oxide composite antibacterial agent dispersion against Escherichia coli is 99.5%.

Example 2

Add 0.008 mol zinc sulfate heptahydrate to a mixed solution of 0.032 mol sodium hydroxide and 0.03 mol urea, add 0.024 mol trisodium citrate, and 40 g deionized water, and react at 50°C for 1 hour. After the reaction is complete, wash several times with clean water. , and then dried to obtain nano zinc oxide.

Put honeysuckle and soluble starch into a cell-level ultrafine grinder (the mass of honeysuckle is equal to the mass of soluble starch), grind at -10°C for 5 minutes to prepare nano-sized Chinese herbal medicine powder.

Add 10% water-soluble polycarboxylic acid to water to dissolve, and divide into 2 parts of equal volume. Add nano-zinc oxide with a mass ratio of 1% to one part, add equal mass of nano-Chinese herbal powder, and add 1% EDC and 1% NHS at the same time to obtain the first solution; add 10% inorganic layered silicate The dispersant is added to another portion and homogenized until all the inorganic layered silicate dispersants are fully contacted with water to completely form a transparent colloid to obtain a second solution; finally, the first solution and the second solution are mixed and homogenized. quality. Preparation of nano-zinc oxide composite antibacterial agent dispersion.

The 1-minute antibacterial rate of the nano zinc oxide composite antibacterial agent dispersion against Escherichia coli is 99.9%.

Example 3

Add 0.008 mol zinc sulfate heptahydrate to a mixed solution of 0.032 mol sodium hydroxide and 0.02 mol urea, add 0.032 mol sodium malate, and 40 g deionized water, and react at 80°C for 1 hour. After the reaction is complete, wash it several times with clean water. Then dry it to obtain nano zinc oxide.

Put Scutellaria baicalensis, Forsythia suspensa and soluble starch into a cell-level ultrafine grinder (the total mass of Scutellaria baicalensis and Forsythia suspensa is equal to the mass of soluble starch), and grind at -10°C for 5 minutes to prepare nano-sized Chinese herbal medicine powder.

Add 10% water-soluble polycarboxylic acid to water to dissolve, and divide it into 2 parts of equal volume. Add nano-zinc oxide with a mass ratio of 1% to one part, add equal mass of nano-Chinese herbal medicine powder, and add 1% EDC and 1% NHS at the same time to obtain the first solution; add 5% inorganic layered silicate The dispersant is added to another portion and homogenized until all the inorganic layered silicate dispersants are fully contacted with water to completely form a transparent colloid to obtain a second solution; finally, the first solution and the second solution are mixed and homogenized. quality. Preparation of nano-zinc oxide composite antibacterial agent dispersion.

The 1-minute antibacterial rate of the nano zinc oxide composite antibacterial agent dispersion against Escherichia coli is 99.0%.

Claims (4)

1. A method for preparing nano zinc oxide composite antibacterial agent dispersion, which is characterized by comprising the following steps: Add water-soluble polycarboxylic acid to water to dissolve, divide it into 2 parts of equal volume, add nano zinc oxide to one part, add equal mass of nano Chinese herbal medicine powder, and add 1-(3-dimethylaminopropyl) at the same time -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide to obtain the first solution; add the inorganic layered silicate dispersant to another portion, homogenize, wait until all the inorganic layers The silicate dispersant is fully contacted with water to completely form a transparent colloid to obtain a second solution; finally, the first solution and the second solution are mixed and homogeneous; the proportion of the water-soluble polycarboxylic acid is 5-50wt% , nano zinc oxide antibacterial agent accounts for 3-20wt%, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide account for 0.5-5wt% , the inorganic layered silicate dispersant accounts for 0-10wt%, the balance is water, and the total amount is 100wt%; The preparation method of nano-zinc oxide includes the following steps: adding zinc source to a mixed solution of sodium hydroxide and urea, adding a complexing agent, reacting at 40-90°C, and adding the zinc source to the mixed solution of sodium hydroxide and urea. The molar ratio of sodium hydroxide to the zinc source is 4:1, and the complexing agent is one of disodium citrate, trisodium citrate, sodium malate or sodium tartrate, and the molar amount is 5% of the zinc source - 50%. 2. The preparation method of a nano zinc oxide composite antibacterial agent dispersion according to claim 1, characterized in that the Chinese herbal medicine is one or more of dandelion, honeysuckle, coptis, Phellodendron, skullcap or forsythia. 3. A method for preparing a nanometer zinc oxide composite antibacterial agent dispersion according to claim 1, characterized in that the nanometer Chinese herbal medicine preparation method is: adding Chinese herbal medicine powder of equal mass to soluble starch or soluble maltodextrin. Put it into a cell-grade ultrafine grinder and grind at low temperature for 2-10 minutes. 4. Application of the nano zinc oxide composite antibacterial agent dispersion prepared by the preparation method of any one of claims 1 to 3 in the preparation of antibacterial drugs.