Copper-based nano antibacterial preparation and preparation method thereof

Abstract

The invention discloses a copper-based nano antibacterial preparation and a preparation method thereof, and relates to the field of nano antibacterial materials. The copper-based nano-antibacterial preparation with high activity, broad-spectrum antibacterial effect, long acting and safety is designed by using an in-situ reduction strategy, the copper-based nano-antibacterial preparation is composed of NH2-UiO-66 (Zr) as a carrier and copper oxide nano-particles formed through copper source pre-adsorption and reducing agent reduction, then the copper oxide nano-particles are coated and modified by an amphipathic drug auxiliary material, the size is in a range of 50-500nm, and the copper-based nano-antibacterial preparation is prepared by using the amphipathic drug auxiliary material to prepare the copper-based nano-antibacterial preparation. The copper content is 5%-40% wt, the compound shows a remarkable antibacterial effect on six clinical drug-resistant bacteria, and the effective antibacterial concentrations are 20 ppm and 60 ppm respectively. Compared with copper oxide and cuprous oxide with the same molar concentration, the antibacterial effects of the antibacterial preparation on escherichia coli and staphylococcus aureus are improved by 8 times and 13 times or above respectively. The antibacterial preparation provided by the invention solves the problem of high dosage of ion antibiosis, and provides an optional way for prevention and treatment of drug-resistant bacterium infection.

Description

Technical Field

[0001] The present invention relates to the field of nano antibacterial materials, in particular to a copper-based nano antibacterial preparation and a preparation method thereof. Background Art

[0002] The global impact of drug-resistant bacterial infections is increasing year by year, ranked fifth among the world's top ten health threats by the World Health Organization (WHO) and posing a threat to human health and safety. In the face of the advent of the "post-antibiotic era," developing novel antimicrobial design strategies is essential to maintaining our advantage in the fight against microorganisms.

[0003] Metal ions play a crucial role in antimicrobial efficacy. Certain metal ions are essential for the functioning of certain enzymes in organisms and are crucial for their survival. However, they also exhibit homeostatic effects, meaning that metal ions can produce toxic side effects beyond a certain concentration. Currently, metals with known antimicrobial properties include first-period transition metals (iron, cobalt, nickel, etc.) and coinage metals (copper, silver, gold). Copper and silver are the most widely used and have a long history of use, with some products approved by the US Food and Drug Administration (FDA). Currently, metal ions are widely used in antimicrobial applications, primarily in the form of direct ionic agents, alloys, metal oxides, and metal compounds. Direct ionic antimicrobial agents, such as Bordeaux mixture, are widely used. Copper and copper-modified alloy surfaces also exhibit significant inhibitory effects on bacterial growth. Metal compounds are an emerging class of antimicrobial agents that play a crucial role in antimicrobial processes and represent a key method for metal ion modification. Some metals and metal compounds possess antimicrobial properties that surpass those of metal ions, such as copper oxychloride (copper oxychloride) and copper hydroxide, which exhibit highly effective antimicrobial effects. Metal oxides also play an important role in the antibacterial process, but their effect is affected by the slow ion release rate. They mostly act as catalysts in the Fenton reaction process and play a role in the antibacterial process.

[0004] Ionic antimicrobial agents require high doses of ions, and metal particles also require high doses to exert effective antimicrobial effects. Metal ion antimicrobial therapy is short-lived and poses safety concerns. Therefore, the design and development of low-dose, long-lasting, and safe metal antimicrobial agents is a major challenge currently faced. Summary of the Invention

[0005] The present invention selects NH2-UiO-66(Zr) nanoparticles with porous structure, large specific surface area, amino surface and intrinsic hydrolase activity as carriers of copper nanoparticles to prepare this new type of metal nano antibacterial preparation with high activity, broad spectrum antibacterial effect, long-term safety. xO(0<x<2) nanoparticles, a copper-based nano antibacterial preparation with in-situ loaded copper oxide was designed and coated with the pharmaceutical excipient Pluronic F127 to improve the dissolution and dispersion of the metal nano antibacterial preparation.

[0006] The method used for the copper-based nano antibacterial preparation of the present invention is that copper ions are pre-adsorbed on the carrier NH2-UiO-66(Zr), then in-situ reduced by a reducing agent, and then coated and modified with an amphiphilic drug excipient. The specific steps are as follows:

[0007] Step 1 Preparation of the carrier

[0008] For this reaction, the materials are weighed according to the molar ratio of zirconium source: ligand: capping agent: reaction solvent = 1-2: 2-4: 400-800: 500-1000, and fully mixed; then a hydrothermal reaction is carried out at 110-150 °C for 12-36 hours; after the reaction, according to the reaction system: washing solvent = 1: 1-3 v / v, acetonitrile and methanol are respectively used for washing three times, and centrifuged at 6000-10000 rpm to discard the supernatant. The precipitate is the prepared carrier; and it is dried at 30-60 °C for 8-24 hours, and then dried in an inert gas (such as nitrogen) atmosphere at 110-150 °C for 2-8 hours to obtain the dried carrier; among them, the zirconium source is a zirconium-containing substance such as zirconium oxychloride octahydrate, zirconium tetrachloride, etc.; the ligand is an organic molecule with two carboxyl ends such as 2-aminoterephthalic acid; the capping agent is an organic molecule containing a single carboxyl such as benzoic acid, acetic acid, etc.; the reaction solvent is N,N-dimethylformamide (DMF).

[0009] Step 2 Synthesis of the copper-based nano antibacterial preparation

[0010] Weigh the synthesis raw materials according to the ratio of carrier: copper source: reducing agent: reaction solvent = 1-2 mol: 5-10 mol: 20-40 mol: 3-6 L, uniformly mix and react at 10-30 °C for 10-60 minutes, centrifuge at 6000-12000 rpm, discard the supernatant, and the lower layer precipitate obtained is the copper-based nano antibacterial preparation of the present invention; then, successively wash three times with methanol-acetonitrile-methanol-ultrapure water according to the reaction system: washing solvent = 1: 1-3 v / v, and vacuum dry or freeze dry for 8-24 hours to obtain the finally dried copper-based nano antibacterial preparation; among them, the carrier is the carrier synthesized in step 1; the copper source used is a copper-containing substance such as copper acetylacetonate, copper chloride, copper sulfate, copper nitrate, etc.; the reducing agent is a reducing substance such as sodium borohydride, hydrazine hydrate, etc.; the reaction solvent is methanol.

[0011] Step 3 Coating of the copper-based nano antibacterial preparation

[0012] Materials are weighed according to a ratio of copper-based nano-antibacterial preparation: amphiphilic drug excipient: reaction solvent = 1 g: 1-5 g: 1-5 L, thoroughly mixed in the reaction solvent, stirred at 10-30° C. for 10-60 minutes, centrifuged at 6000-10000 rpm, and the supernatant is discarded. After obtaining the precipitate, it is washed three times with ultrapure water according to a reaction system: washing solvent = 1: 1-3 v / v, and then vacuum dried or freeze-dried for 8-24 hours to obtain a surface-coated copper-based nano-antibacterial preparation; wherein the copper-based nano-antibacterial preparation is the final substance prepared in step 2; the amphiphilic drug excipient is Pluronic F127; and the reaction solvent is methanol. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is a transmission electron microscope (TEM) image of the copper-based nano-antibacterial preparation prepared in the present invention, including a) a copper-based nano-antibacterial preparation carrier, b) a copper-based nano-antibacterial preparation and c) a copper-based nano-antibacterial preparation coated with a pharmaceutical excipient.

[0014] Figure 2 The antibacterial effect of the copper-based nano antibacterial preparation prepared in the present invention on four Gram-negative bacteria (a Escherichia coli, b Pseudomonas aeruginosa, c Acinetobacter baumannii, d Klebsiella pneumoniae) was tested.

[0015] Figure 3 The antibacterial effect of the copper-based nano antibacterial preparation prepared in the present invention on two Gram-positive bacteria (a Staphylococcus aureus and b Enterococcus faecalis) was tested. DETAILED DESCRIPTION

[0016] Example 1 Preparation and characterization of copper-based nano antibacterial preparations

[0017] 1) Preparation of NH2-UiO-66(Zr) as a carrier for copper-based nano-antibacterial preparations

[0018] The materials were weighed and mixed thoroughly according to the ratio of zirconium chloride octahydrate: 2-aminoterephthalic acid: benzoic acid: N,N-dimethylformamide (DMF) = 600 mg: 600 mg: 12.5 g: 100 mL; placed in a 200 mL reactor and reacted at 120° C. for 24 hours; after the reaction, according to the reaction system: washing solvent = 1:3 v / v, washed three times with acetonitrile and methanol respectively, centrifuged at 8000 rpm, and the supernatant was discarded to obtain the carrier NH2-UiO-66 (Zr); and vacuum dried at 60° C. for 12 hours, and then dried at 120° C. in a nitrogen atmosphere for 2 hours to obtain the dried carrier NH2-UiO-66 (Zr). The prepared NH2-UiO-66(Zr) carrier was tested using Zetasizer NanoZS. The test results showed that the particle size was 84nm±5nm, the PDI value was 0.18, and the surface potential was 30.1mV. The morphology was observed using a transmission electron microscope (Hitachi HT7800). The specific results are as follows: Figure 1 a.

[0019] 2) Copper-based nano antibacterial preparations Cu x Synthesis of O / NH2-UiO-66(Zr)

[0020] The materials were weighed according to the ratio of NH2-UiO-66(Zr): copper acetylacetonate: sodium borohydride: methanol = 5 mg: 7 mg: 3 mg: 10 mL and stirred thoroughly. The mixture was stirred and reacted at 25 ° C for 30 minutes, centrifuged at 8000 rpm, and the supernatant was discarded to obtain the lower precipitate. Then, the mixture was washed three times with methanol-acetonitrile-methanol-ultrapure water according to the reaction system: washing solvent = 1:3 v / v, and freeze-dried for 12 hours to obtain a copper-based nano antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr). The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size 87nm±6nm, PDI value 0.16, surface potential 10.2mV, and morphology was observed using a transmission electron microscope (Hitachi HT7800). The specific results are as follows Figure 1 b. The copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), which was 11.3% wt. X-ray photoelectron spectroscopy (XPS) and X-ray diffractometer (XRD) test results showed that copper existed in a mixed valence state.

[0021] 3) Copper-based nano antibacterial preparations coated with drug excipients Cu x Preparation of O / NH2-UiO-66(Zr)@F127

[0022] Pluronic F127 was added according to the ratio of copper-based nano-antibacterial preparation: Pluronic F127 = 1:1wt, stirred at 25°C for 30 minutes, washed three times with ultrapure water according to the reaction system: washing solvent = 1:3v / v, and then freeze-dried for 12 hours to prepare the coated copper-based nano-antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr)@F127. The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size 103nm±8nm, PDI value 0.22, surface potential 8.4mV, and morphology was observed using a transmission electron microscope (Hitachi HT7800). The specific results are as follows Figure 1 c, and the copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), which was 10.8% wt. The test results of X-ray photoelectron spectroscopy (XPS) and X-ray diffractometer (XRD) showed that copper existed in a mixed valence state.

[0023] 4) Characterization of antibacterial properties of copper-based nano-antibacterial preparations

[0024] The antibacterial effect test was carried out in accordance with the "Health Industry Standard of the People's Republic of China" (WS / T 650-2019), and the antibacterial effect test was carried out on 4 Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae) and 2 Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis). The results showed that: Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae) at a concentration of 60 ppm. Figure 2 );Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) at a concentration of 20 ppm (e.g. Figure 3 Compared with copper oxide and cuprous oxide at the same molar concentration, the copper-based nano antibacterial preparations increased the activity against Escherichia coli and Staphylococcus aureus by more than 8 times and 13 times, respectively.

[0025] Example 2 Preparation and Characterization of Copper-Based Nano-Antibacterial Preparations

[0026] 1) Preparation of NH2-UiO-66(Zr) as a carrier for copper-based nano-antibacterial preparations

[0027] The materials were weighed and thoroughly mixed in a 200-mL reaction vessel (500 mg zirconium oxychloride octahydrate, 600 mg 2-aminoterephthalic acid, 10 g benzoic acid, and 100 mL N,N-dimethylformamide (DMF). The mixture was reacted at 120°C for 24 hours. After the reaction, the mixture was washed three times with acetonitrile and methanol, respectively, using a reaction system of 1:3 v / v washing solvent. The mixture was centrifuged at 8000 rpm, and the supernatant was discarded to prepare the NH2-UiO-66(Zr) support. The prepared NH2-UiO-66(Zr) support was then vacuum-dried at 60°C for 12 hours and then dried at 120°C under nitrogen for 2 hours. The prepared NH2-UiO-66(Zr) support was tested using a Zetasizer NanoZS, revealing a particle size of 110 nm ± 7 nm, a PDI of 0.21, and a surface potential of 30.5 mV.

[0028] 2) Copper-based nano antibacterial preparations Cu x Synthesis of O / NH2-UiO-66(Zr)

[0029] The materials were weighed according to the ratio of NH2-UiO-66(Zr): copper acetylacetonate: sodium borohydride: methanol = 5 mg: 7 mg: 3 mg: 10 mL and stirred thoroughly. The mixture was stirred and reacted at 25 ° C for 30 minutes, centrifuged at 8000 rpm, and the supernatant was discarded to obtain the lower precipitate. Then, the mixture was washed three times with methanol-acetonitrile-methanol-ultrapure water according to the reaction system: washing solvent = 1:3 v / v, and freeze-dried for 12 hours to obtain a copper-based nano antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr). The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size was 116nm±5nm, PDI value was 0.18, surface potential was 11.4mV, and the copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), and its content was 10.2%wt. The test results of X-ray photoelectron spectrometry (XPS) and X-ray diffractometer (XRD) showed that copper existed in a mixed valence state.

[0030] 3) Copper-based nano antibacterial preparations coated with drug excipients Cu x Preparation of O / NH2-UiO-66(Zr)@F127

[0031] Pluronic F127 was added according to the ratio of copper-based nano-antibacterial preparation: Pluronic F127 = 1:1.5wt, stirred at 25°C for 30 minutes, washed three times with ultrapure water according to the reaction system: washing solvent = 1:3v / v, and then freeze-dried for 12 hours to prepare the coated copper-based nano-antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr)@F127. The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size was 121nm±5nm, PDI value was 0.24, surface potential was 9.2mV, and the copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), which was 9.7%wt. The test results of X-ray photoelectron spectrometry (XPS) and X-ray diffractometer (XRD) showed that copper existed in a mixed valence state.

[0032] 4) Characterization of antibacterial properties of copper-based nano-antibacterial preparations

[0033] The antibacterial effect test was carried out in accordance with the "Health Industry Standard of the People's Republic of China" (WS / T 650-2019), and the antibacterial effect test was carried out on 4 Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae) and 2 Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis). The results showed that: Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae) at a concentration of 60 ppm; Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) at a concentration level of 20 ppm.

[0034] Example 3 Preparation and characterization of copper-based nano antibacterial preparations

[0035] 1) Preparation of NH2-UiO-66(Zr) as a carrier for copper-based nano-antibacterial preparations

[0036] The materials were weighed and thoroughly mixed in a 200-mL reaction vessel at a ratio of 1370 mg zirconium tetrachloride: 600 mg 2-aminoterephthalic acid: 12.5 g benzoic acid: 100 mL N,N-dimethylformamide (DMF). The mixture was reacted at 120°C for 24 hours. After completion of the reaction, the mixture was washed three times with acetonitrile and methanol, respectively, using a reaction system of 1:3 v / v washing solvent. The mixture was centrifuged at 8000 rpm, and the supernatant was discarded to prepare the NH2-UiO-66(Zr) support. The prepared NH2-UiO-66(Zr) support was then vacuum-dried at 60°C for 12 hours and then dried at 120°C under nitrogen for 2 hours. The prepared NH2-UiO-66(Zr) support was tested using a Zetasizer NanoZS, revealing a particle size of 86 nm ± 4 nm, a PDI value of 0.12, and a surface potential of 28.0 mV.

[0037] 2) Copper-based nano antibacterial preparations Cu x Synthesis of O / NH2-UiO-66(Zr)

[0038] The materials were weighed according to the ratio of NH2-UiO-66(Zr): copper nitrate: sodium borohydride: methanol = 5 mg: 5 mg: 3 mg: 10 mL and stirred thoroughly. The mixture was stirred at 25 ° C for 30 minutes, centrifuged at 8000 rpm, and the supernatant was discarded to obtain the lower precipitate. Then, according to the reaction system: washing solvent = 1: 3 v / v, methanol-acetonitrile-methanol-ultrapure water was used for three times of washing, and freeze-dried for 24 hours to obtain a copper-based nano antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr). The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size was 90nm±5nm, PDI value was 0.13, surface potential was 11.6mV, and the copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), and its content was 11.0%wt. The test results of X-ray photoelectron spectrometry (XPS) and X-ray diffractometer (XRD) showed that copper existed in a mixed valence state.

[0039] 3) Copper-based nano antibacterial preparations coated with drug excipients Cu x Preparation of O / NH2-UiO-66(Zr)@F127

[0040] Pluronic F127 was added according to the ratio of copper-based nano-antibacterial preparation: Pluronic F127 = 1:2wt, stirred at 25°C for 30 minutes, washed three times with ultrapure water according to the reaction system: washing solvent = 1:3v / v, and then freeze-dried for 12 hours to prepare the coated copper-based nano-antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr)@F127. The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size of 105nm±5nm, PDI value of 0.19, surface potential of 8.7mV, and copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), which was 10.5%wt. X-ray photoelectron spectrometer (XPS) and X-ray diffractometer (XRD) test results showed that copper existed in a mixed valence state.

[0041] 4) Characterization of antibacterial properties of copper-based nano-antibacterial preparations

[0042] The antibacterial effect test was carried out in accordance with the "Health Industry Standard of the People's Republic of China" (WS / T 650-2019), and the antibacterial effect test was carried out on 4 Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae) and 2 Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis). The results showed that: Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae) at a concentration of 60 ppm; Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) at a concentration level of 20 ppm.

[0043] Example 4 Preparation and Characterization of Copper-Based Nano-Antibacterial Preparations

[0044] 1) Preparation of NH2-UiO-66(Zr) as a carrier for copper-based nano-antibacterial preparations

[0045] The materials were weighed and mixed thoroughly according to the ratio of zirconium chloride octahydrate: 2-aminoterephthalic acid: benzoic acid: N,N-dimethylformamide (DMF) = 600 mg: 600 mg: 12.5 g: 100 mL; placed in a 200 mL reactor and reacted at 120° C. for 24 hours; after the reaction, according to the reaction system: washing solvent = 1:3 v / v, washed three times with acetonitrile and methanol respectively, centrifuged at 8000 rpm, and the supernatant was discarded to obtain the carrier NH2-UiO-66 (Zr); and vacuum dried at 60° C. for 12 hours, and then dried at 120° C. in a nitrogen atmosphere for 2 hours to obtain the dried carrier NH2-UiO-66 (Zr). The prepared NH2-UiO-66(Zr) carrier was tested using Zetasizer NanoZS. The test results showed that the particle size was 84nm±5nm, the PDI value was 0.18, and the surface potential was 30.1mV. The morphology was observed using a transmission electron microscope (Hitachi HT7800). The specific results are as follows: Figure 1 a.

[0046] 2) Copper-based nano antibacterial preparations Cu x Synthesis of O / NH2-UiO-66(Zr)

[0047] The materials were weighed according to the ratio of NH2-UiO-66(Zr): copper nitrate: sodium borohydride: methanol = 5 mg: 25 mg: 15 mg: 10 mL and stirred thoroughly. The mixture was stirred and reacted at 25 ° C for 30 minutes, centrifuged at 8000 rpm, and the supernatant was discarded to obtain the lower precipitate. Then, according to the reaction system: washing solvent = 1: 3 v / v, methanol-acetonitrile-methanol-ultrapure water was used for washing three times, and freeze-dried for 12 hours to obtain a copper-based nano antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr). The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size was 89nm±5nm, PDI value was 0.14, surface potential was 11.6mV, and the copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), and its content was 23.0%wt. The test results of X-ray photoelectron spectrometry (XPS) and X-ray diffractometer (XRD) showed that copper existed in a mixed valence state.

[0048] 3) Copper-based nano antibacterial preparations coated with drug excipients Cu x Preparation of O / NH2-UiO-66(Zr)@F127

[0049] Pluronic F127 was added according to the ratio of copper-based nano-antibacterial preparation: Pluronic F127 = 1:1wt, stirred at 25°C for 30 minutes, washed three times with ultrapure water according to the reaction system: washing solvent = 1:3v / v, and then freeze-dried for 12 hours to prepare the coated copper-based nano-antibacterial preparation, referred to as Cu x O / NH2-UiO-66(Zr)@F127. The prepared Cu x The O / NH2-UiO-66(Zr) carrier was tested, and the test results were: particle size was 93nm±7nm, PDI value was 0.22, surface potential was 10.2mV, and the copper content was determined by inductively coupled plasma mass spectrometry (ICP-MS), and its content was 22.6%wt. The test results of X-ray photoelectron spectrometry (XPS) and X-ray diffractometer (XRD) showed that copper existed in a mixed valence state.

[0050] 4) Characterization of antibacterial properties of copper-based nano-antibacterial preparations

[0051] The antibacterial effect test was carried out in accordance with the "Health Industry Standard of the People's Republic of China" (WS / T 650-2019), and the antibacterial effect test was carried out on 4 Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae) and 2 Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis). The results showed that: Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae) at a concentration of 30 ppm; Cu x O / NH2-UiO-66(Zr)@F127 has an antibacterial effect of more than 99.00% against two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) at a concentration level of 10 ppm.

[0052] The present invention is not limited to the above-mentioned embodiments. Any modification, improvement, or substitution that can be conceived by those skilled in the art without departing from the essence of the present invention falls within the scope of the present invention.

Claims

1. A copper-based nano antibacterial preparation, characterized in that: The copper-based nano antibacterial preparation is composed of NH2-UiO-66 as a carrier and copper oxide nanoparticles formed by pre-adsorption of a copper source and reduction with a reducing agent, and is then coated and modified with an amphiphilic drug excipient.

2. The method for preparing the copper-based nano antibacterial preparation according to claim 1, characterized in that: Copper ions are pre-adsorbed on the carrier NH2-UiO-66, then reduced in situ by a reducing agent, and then coated with amphiphilic drug excipients. The specific synthesis method is as follows: The synthesis method of NH2-UiO-66, a carrier constituting a copper-based nano-antibacterial preparation, is a hydrothermal method. The specific process comprises preparing raw materials at a molar ratio of zirconium source: ligand: end-capping agent: reaction solvent = 1-2: 2-4: 400-800: 500-1000, fully dissolving, placing in a reaction kettle, and reacting for 12-36 hours at 110-150°C and 20-101.3kPa. The zirconium source is zirconium oxychloride octahydrate or zirconium tetrachloride; the ligand is 2-aminoterephthalic acid; the end-capping agent is benzoic acid, acetic acid, or formic acid; and the reaction solvent is N,N-dimethylformamide. The copper oxide nanoparticle synthesis method is an in-situ reduction method. The specific synthesis process is as follows: synthetic raw materials are weighed according to the ratio of carrier: copper source: reducing agent: reaction solvent = 1-2 mol: 5-10 mol: 20-40 mol: 3-6 L, mixed evenly, reacted at 10-30 ° C for 10-60 minutes, centrifuged at 6000-12000 rpm, and the supernatant is discarded to obtain the lower layer precipitate, which is the copper-based nano-antibacterial preparation; then, it is washed with methanol-acetonitrile-methanol-ultrapure water in sequence, and vacuum dried or freeze-dried for 8-24 hours to obtain the final dry copper-based nano-antibacterial preparation; wherein the copper source is copper acetylacetonate, copper chloride, copper sulfate, or copper nitrate; the reducing agent is sodium borohydride or hydrazine hydrate; and the reaction solvent is methanol. The specific process of coating and modifying the amphiphilic drug excipient is as follows: weighing materials according to the ratio of copper-based nano-antibacterial preparation: amphiphilic drug excipient: reaction solvent = 1g:1-5g:1-5L, fully mixing in the reaction solvent, stirring at 10-30°C for 10-60 minutes, centrifuging at 6000-10000 rpm, discarding the supernatant, obtaining the precipitate, washing with ultrapure water, and then vacuum drying or freeze-drying for 8-24 hours to obtain the surface-coated copper-based nano-antibacterial preparation; wherein the amphiphilic drug excipient is Pluronic F127; and the reaction solvent is methanol.

3. The copper-based nano antibacterial preparation according to claim 1, characterized in that The molecular formula of the carrier NH2-UiO-66 that constitutes the copper-based nano antibacterial preparation is C 48 H 34 N6O 32 Zr6, size is 50-500nm.

4. The copper-based nano antibacterial preparation according to claim 1, characterized in that The copper oxide nanoparticles that make up the copper-based nano antibacterial preparation have a molecular formula of Cu x O0 < x < 2, with a size in the range below 15 nanometers and a copper content in the range of 5%-40% wt.

5. The copper-based nano antibacterial preparation prepared by the method according to claim 2.

6. The carrier NH2-UiO-66 prepared by the method according to claim 2.

7. Copper oxide nanoparticles prepared by the method according to claim 2.

Images