CN118141936A - Self-delivery nano antibacterial agent and preparation method thereof - Google Patents

Self-delivery nano antibacterial agent and preparation method thereof Download PDF

Info

Publication number
CN118141936A
CN118141936A CN202410231101.3A CN202410231101A CN118141936A CN 118141936 A CN118141936 A CN 118141936A CN 202410231101 A CN202410231101 A CN 202410231101A CN 118141936 A CN118141936 A CN 118141936A
Authority
CN
China
Prior art keywords
nano
antibacterial
self
antimicrobial agent
emodin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202410231101.3A
Other languages
Chinese (zh)
Inventor
曾伟深
林晓程
崔汝婷
郭宁
刘允
许伟森
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dongguan Eighth People's Hospital (dongguan Children's Hospital)
Original Assignee
Dongguan Eighth People's Hospital (dongguan Children's Hospital)
Filing date
Publication date
Application filed by Dongguan Eighth People's Hospital (dongguan Children's Hospital) filed Critical Dongguan Eighth People's Hospital (dongguan Children's Hospital)
Publication of CN118141936A publication Critical patent/CN118141936A/en
Pending legal-status Critical Current

Links

Abstract

The invention relates to the technical field of antibacterial materials, in particular to a self-delivery nano antibacterial agent and a preparation method thereof, wherein the nano antibacterial agent comprises the following components: the antibacterial traditional Chinese medicine composition comprises antibiotics, traditional Chinese medicine active ingredients with antibacterial action and terephthalylboronic acid, wherein the antibiotics are any one of sulfadiazine (Sulfadiazine, SD), sulfadimidine (Sulfadimidine, SMD), sulfamethoxazole (Sulfamethoxazole, SMX) and sulfaisoxazole (Sulfisoxazole, SSD), and the traditional Chinese medicine active ingredients with antibacterial action are any one of emodin (rheum emodin, RE), aloe-emodin (AE), chrysophanol (chrysophanic acid, CA) and rhein (RHEINIC ACID, RA).

Description

Self-delivery nano antibacterial agent and preparation method thereof
Technical Field
The invention relates to the technical field of antibacterial materials, in particular to a self-delivery nano antibacterial agent and a preparation method thereof.
Background
Antibiotics are antibacterial substances which inhibit the growth of microorganisms or kill microorganisms, and have been widely used for treating bacterial infections in humans and animals since their high-efficiency and spectral antibacterial characteristics have been found, however, abuse of antibiotics is inducing the appearance of more and more resistant bacteria, more and more common antibiotics lose their original efficacy with the acceleration of bacterial resistance, antibiotics obtained by chemical structural modification of existing antibiotics also rapidly develop resistance in a short period, and the development of novel antibiotics requires high cost and time, the speed of bacterial obtaining resistance has far exceeded the speed of development of new drugs, and the problem of antibiotic resistance is difficult and impossible to overcome due to the action mechanism of antibiotics and bacterial evolution, however, some methods can be used to reduce the appearance and influence of resistance.
In the treatment of bacterial infection, the combined use of antibiotics and other compounds is a potential method for overcoming the drug resistance of bacteria, and by reducing the dosage of each compound, the combined use can overcome the toxicity and other side effects related to single drug used at high dosage, reduce the clinical drug risk, is an effective clinical treatment scheme, and the traditional Chinese medicine has the characteristics of naturalness, economy, safety, difficulty in causing the drug resistance of bacteria, and the like, has become a research hotspot of antibacterial drugs, and researches find that a plurality of traditional Chinese medicine active ingredients have a certain inhibition effect on the drug resistance bacteria.
Targeting and controlled release of antibacterial drugs to bacterial infection sites remains a major challenge, this strategy can improve selectivity and bioavailability of drugs while reducing toxicity, bacterial membrane surfaces have cis-dihydroxyl-containing teichoic acid or lipoglycan, and phenylboronic acid and derivatives thereof contain boric acid groups which can be covalently bound with molecules with cis-diol groups to form boric acid esters, therefore phenylboronic acid and derivatives thereof can be used as bacterial targeting agents, and covalently bound with teichoic acid or lipoglycan on bacterial membrane surfaces to form boric acid esters, thus realizing bacterial targeting adhesion, and the formed boric acid esters have pH responsiveness, can accelerate hydrolysis under the micro-acid environment of bacterial infection sites, release antibacterial drugs to exert efficacy, thus achieving the purpose of targeted release of antibacterial drugs.
Disclosure of Invention
The invention aims to solve the defects in the background technology and provides a self-delivery nano antibacterial agent and a preparation method thereof.
In order to achieve the above purpose, the invention adopts the following technical scheme: a self-delivering nano-antimicrobial agent, the nano-antimicrobial agent consisting of: antibiotics, chinese medicinal active ingredients with antibacterial effect and terephthalonitrile.
Preferably, the antibiotic is any one of sulfadiazine (Sulfadiazine, SD), sulfadimidine (Sulfadimidine, SMD), sulfamethoxazole (Sulfamethoxazole, SMX) and sulfaisoxazole (Sulfisoxazole, SSD).
Preferably, the Chinese medicinal active ingredient with antibacterial effect is any one of emodin (rheum emodin, RE), aloe-emodin (AE), chrysophanol (chrysophanic acid, CA) and rhein (RHEINIC ACID, RA).
Preferably, a method for preparing a self-delivery nano-antimicrobial agent is characterized by comprising the following steps: the preparation method comprises the following preparation steps:
S1, weighing 0.1mmol of antibiotics, traditional Chinese medicine active ingredients and terephthaloyl (1, 4-PBA) and respectively dissolving in 1mL of DMSO;
S2, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuing stirring and reacting for 4h;
S3, after the reaction is finished, dialyzing with deionized water for 1 day (300 Da) to remove unassembled materials;
s4, centrifuging at 3000rpm for 10min, collecting supernatant, lyophilizing to obtain the nanometer antibacterial agent, and storing at-20deg.C.
Compared with the prior art, the invention has the following beneficial effects:
The antibiotic and the traditional Chinese medicine active ingredient have the antibacterial effect through the synergistic effect of the components of the self-delivery nano antibacterial agent, the toxicity and other side effects related to the single medicine used at a high dose can be overcome by combined administration of the antibiotic and the traditional Chinese medicine active ingredient, in addition, the combined use of the antibiotic and the traditional Chinese medicine ingredient is expected to reverse the drug resistance of bacteria to the antibiotic, so that the bacteria are re-sensitized to the antibiotic, the treatment effect of the antibiotic is indirectly enhanced, the terephthalyl acid in the prodrug can be covalently combined with the surface of a bacterial membrane to form a boric acid ester bond, the antibacterial nano ion prodrug is targeted to the surface of the bacteria, the high antibacterial efficiency is obtained at a low dose, the normal tissue cells cannot be toxic, and finally, the boric acid ester bond is hydrolyzed under the condition of micro-acid environment of bacterial infection, the antibiotic and the traditional Chinese medicine active ingredient are released, so that the antibacterial effect is realized.
Drawings
FIG. 1 is a schematic illustration of the preparation process and bacteriostasis of a self-delivering nano-antimicrobial agent and a preparation method thereof according to the present invention;
FIG. 2 is a transmission electron microscope image of the nano-antimicrobial agent prepared in example 1 of the self-delivering nano-antimicrobial agent and the preparation method thereof according to the present invention;
FIG. 3 is an infrared spectrum of the nano-antimicrobial agent prepared in example 1 of the self-delivering nano-antimicrobial agent and the preparation method thereof according to the present invention;
FIG. 4 is a coated sheet and bar chart showing the effect of the nano-antimicrobial agent prepared in example 1 of the self-delivering nano-antimicrobial agent and the preparation method thereof against Staphylococcus aureus and Escherichia coli under different conditions;
FIG. 5 is a graph showing cytotoxicity of the nano-antimicrobial agent prepared in example 1 of the self-delivering nano-antimicrobial agent and the preparation method thereof according to the present invention at different concentrations;
FIG. 6 is a graph showing the hemolysis test of the nano-antimicrobial agent prepared in example 1 of the self-delivering nano-antimicrobial agent and the preparation method thereof under different concentrations.
Detailed Description
The following description is presented to enable one of ordinary skill in the art to make and use the invention. The preferred embodiments in the following description are by way of example only and other obvious variations will occur to those skilled in the art.
A self-delivering nano-antimicrobial agent as shown in fig. 1 and a method for preparing the same comprises the following examples:
Example 1:
A self-delivering nano-antimicrobial agent, the nano-antimicrobial agent consisting of: antibiotics, chinese medicinal active ingredients with antibacterial effect and terephthalonitrile.
The antibiotic is sulfadiazine (Sulfadiazine, SD).
The Chinese medicinal active ingredient with antibacterial effect is emodin (rheum emodin, RE).
The preparation method of the self-delivery nano antibacterial agent comprises the following preparation steps:
s1, weighing 0.1mmol of SD, RE and 1,4-PBA, and respectively dissolving in 1mL of DMSO;
S2, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuing stirring and reacting for 4h;
S3, after the reaction is finished, dialyzing with deionized water for 1 day (300 Da) to remove unassembled materials;
s4, centrifuging at 3000rpm for 10min, collecting supernatant, lyophilizing to obtain the nanometer antibacterial agent, and storing at-20deg.C.
Example 2:
A self-delivering nano-antimicrobial agent, the nano-antimicrobial agent consisting of: antibiotics, chinese medicinal active ingredients with antibacterial effect and terephthalonitrile.
The antibiotic is sulfadiazine (Sulfadiazine, SD).
The Chinese medicinal active ingredient with antibacterial effect is aloe-emodin (AE).
The preparation method of the self-delivery nano antibacterial agent comprises the following preparation steps:
S1, weighing 0.1mmol of SD, AE and 1,4-PBA, and respectively dissolving in 1mL of DMSO;
S2, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuing stirring and reacting for 4h;
S3, after the reaction is finished, dialyzing with deionized water for 1 day (300 Da) to remove unassembled materials;
s4, centrifuging at 3000rpm for 10min, taking supernatant, freeze-drying to obtain the nano antibacterial agent SD@AE@1,4-PBA, and preserving at-20 ℃ for later use.
Example 3:
A self-delivering nano-antimicrobial agent, the nano-antimicrobial agent consisting of: antibiotics, chinese medicinal active ingredients with antibacterial effect and terephthalonitrile.
The antibiotic is sulfadimidine (Sulfadimidine, SMD).
The Chinese medicinal active ingredient with antibacterial effect is emodin (rheum emodin, RE).
The preparation method of the self-delivery nano antibacterial agent comprises the following preparation steps:
S1, weighing 0.1mmol of SMD, RE and 1,4-PBA, and respectively dissolving in 1mL of DMSO;
S2, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuing stirring and reacting for 4h;
S3, after the reaction is finished, dialyzing with deionized water for 1 day (300 Da) to remove unassembled materials;
s4, centrifuging at 3000rpm for 10min, collecting supernatant, lyophilizing to obtain the nanometer antibacterial agent, and storing at-20deg.C.
Example 4:
A self-delivering nano-antimicrobial agent, the nano-antimicrobial agent consisting of: antibiotics, chinese medicinal active ingredients with antibacterial effect and terephthalonitrile.
The antibiotic is sulfadimidine (Sulfadimidine, SMD).
The Chinese medicinal active ingredient with antibacterial effect is aloe-emodin (AE).
The preparation method of the self-delivery nano antibacterial agent comprises the following preparation steps:
S1, weighing 0.1mmol of SMD, AE and 1,4-PBA, and respectively dissolving in 1mL of DMSO;
S2, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuing stirring and reacting for 4h;
S3, after the reaction is finished, dialyzing with deionized water for 1 day (300 Da) to remove unassembled materials;
s4, centrifuging at 3000rpm for 10min, collecting supernatant, lyophilizing to obtain the nanometer antibacterial agent, and storing at-20deg.C.
As shown in FIG. 2, the nano-antibacterial agent exhibited an irregular spherical shape with a particle diameter of about 81nm.
As shown in FIG. 3, the characteristic peaks of SD, RE, 1,4-PBA and the nano antibacterial agent are analyzed by adopting a Fourier infrared spectrophotometer, and the characteristic absorption peaks of SD, RE and 1,4-PBA of the nano antibacterial agent are obvious, wherein the 1492cm < -1 > is the pyrimidine ring skeleton stretching vibration of SD, and the 3356cm < -1 > is the N-H stretching vibration; the 9 C=10C, 11C=12C, 7C=21O double bond stretching vibration of RE at 1665cm-1 and the B-O stretching vibration of PBA at 1342cm-1 prove the successful synthesis of the nano antibacterial agent.
As shown in FIG. 4, after a single colony of Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli) was picked up and dispersed in LB, cultured at 37℃for 12 hours, diluted with fresh LB liquid medium to a certain concentration (107 CFU/mL), subjected to the following antibacterial test, staphylococcus aureus or Escherichia coli solution (500. Mu.L, 107 CFU/mL) was subjected to the following antibacterial test with a nanoantimicrobial solution (1.5, 1.0, 0.5, 0.25 mg/mL) without glucose or with glucose (10. Mu.g/mL) in pH5.5 and in pH 7.4, shake-cultured at 100rpm in 48 well plates for 4 hours, then 10. Mu.L of the treated bacterial liquid was diluted 1000-fold with 0.9% NaCI, applied to MH solid agar plates, cultured at 37℃for a certain time, and finally, the number of antibacterial Colonies (CFU) was calculated on the solid agar plates, and the following parallel formula was calculated three times for each group, respectively: the antibacterial ratio (%) = (1-material bacterial solution concentration/control bacterial solution concentration), the antibacterial effect of the nano antibacterial agent is obviously different under different treatment conditions, wherein the antibacterial ratio is highest under the conditions of pH5.5 and no glucose, the antibacterial ratio of the nano antibacterial agent is increased along with the increase of the concentration, and when the concentration of the nano antibacterial agent is 1.5mg/ml, the antibacterial ratio of the nano antibacterial agent to S.aureus and E.coli is respectively 84.0% and 88.6%, which indicates that the nano antibacterial agent has better antibacterial effect.
As shown in FIG. 5, the cytotoxicity of the nano-antimicrobial agent against L929 cells was detected by MTT method, and it can be seen from the figure that the cell viability was still more than 90% when the nano-antimicrobial agent concentration was increased to 1.5mg/mL, thereby proving good biosafety.
As shown in FIG. 6, when the mass concentration is not higher than 1.5mg/mL, the hemolysis rate of the nano-antibacterial agent is less than 1% and is lower than 5% of the international standard requirement, thereby further proving that the nano-antibacterial agent has good biocompatibility and safety when the mass concentration is not higher than 1.5 mg/mL.
Working principle:
In actual use, 0.1mmol of antibiotics, chinese medicinal active ingredients and terephthaloyl (1, 4-PBA) are weighed and respectively dissolved in 1mL of DMSO; then, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuously stirring and reacting for 4h; after the reaction was completed, the unassembled material was removed by dialysis against deionized water for 1 day (300 Da); and centrifuging at 3000rpm for 10min, collecting supernatant, freeze-drying to obtain the nano antibacterial agent, storing at-20 ℃ for standby, and carrying out self-transfer of synergistic action of all components of the nano antibacterial agent, wherein the antibiotic and the traditional Chinese medicine active ingredient have antibacterial action, and the combined use of the two components can overcome toxicity and other side effects related to single medicine used at high dosage.
The foregoing has shown and described the basic principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that the above embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made therein without departing from the spirit and scope of the invention, which is defined by the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims (4)

1. A self-delivering nano-antimicrobial agent, characterized in that: the nano antibacterial agent consists of the following components: antibiotics, chinese medicinal active ingredients with antibacterial effect and terephthalonitrile.
2. The self-delivering nano-antimicrobial agent of claim 1, wherein: the antibiotic is any one of sulfadiazine (Sulfadiazine, SD), sulfadimidine (Sulfadimidine, SMD), sulfamethoxazole (Sulfamethoxazole, SMX) and sulfaisoxazole (Sulfisoxazole, SSD).
3. The self-delivering nano-antimicrobial agent of claim 1, wherein: the Chinese medicinal active ingredients with antibacterial effect are any one of emodin (rheum emodin, RE), aloe-emodin (AE), chrysophanol (chrysophanic acid, CA) and rhein (RHEINIC ACID, RA).
4. A method for preparing a self-delivering nano-antimicrobial agent according to any one of claims 1-3, characterized in that: the preparation method comprises the following preparation steps:
S1, weighing 0.1mmol of antibiotics, traditional Chinese medicine active ingredients and terephthaloyl (1, 4-PBA) and respectively dissolving in 1mL of DMSO;
S2, dropwise adding the mixture into 30mL of deionized water at a speed of 4mL/h by adopting a syringe pump, and continuing stirring and reacting for 4h;
S3, after the reaction is finished, dialyzing with deionized water for 1 day (300 Da) to remove unassembled materials;
s4, centrifuging at 3000rpm for 10min, collecting supernatant, lyophilizing to obtain the nanometer antibacterial agent, and storing at-20deg.C.
CN202410231101.3A 2024-02-29 Self-delivery nano antibacterial agent and preparation method thereof Pending CN118141936A (en)

Publications (1)

Publication Number Publication Date
CN118141936A true CN118141936A (en) 2024-06-07

Family

ID=

Similar Documents

Publication Publication Date Title
Shariatinia Carboxymethyl chitosan: Properties and biomedical applications
Gao et al. Near-infrared light-controllable on-demand antibiotics release using thermo-sensitive hydrogel-based drug reservoir for combating bacterial infection
CN101278896B (en) Chitosan nano silver gel agent and uses thereof
Dhanalakshmi et al. Skin and muscle permeating antibacterial nanoparticles for treating Staphylococcus aureus infected wounds
Shariati et al. Graphene-based materials for inhibition of wound infection and accelerating wound healing
CN112294752B (en) AgNPs @ CSSCS nanogel drug-loading system and preparation thereof
Arif et al. Chitosan-based nanoparticles as delivery-carrier for promising antimicrobial glycolipid biosurfactant to improve the eradication rate of Helicobacter pylori biofilm
CN111281976B (en) Preparation method and application of functionalized graphene targeted sterilization material with photo-thermal and chemotherapy synergistic effects
EP0649437B1 (en) Process for the preparation of iodinated biopolymers having disinfectant and cicatrizing activity, and the iodinated biopolymers obtainable thereby
Kenawy et al. Synthesis and biocidal activity of modified poly (vinyl alcohol)
Kanth et al. Recent advancements and perspective of ciprofloxacin-based antimicrobial polymers
CN1843124A (en) Nano silver coating agent for sterilization and its preparation method
CN102405935A (en) Protamine compounded preparation, preparation method and application thereof
CN118141936A (en) Self-delivery nano antibacterial agent and preparation method thereof
CN107137761B (en) Chitin-amphiphilic ion/quaternary ammonium salt natural dressing and preparation method and application thereof
CN115105629B (en) Antibacterial hydrogel and preparation method and application thereof
CN1850113A (en) Amoxicillin antibacterial agent containing nano silver, and its preparing method and use
RU2308970C1 (en) Antibacterial agent for treatment of intracellular infection
Popescu et al. Study of antimicrobial effects of functionalized silver nanoparticles
CN110604822B (en) Magnetic antibacterial nano system and preparation method thereof
Zhang et al. Preparation, characterization, and Staphylococcus aureus biofilm elimination effect of baicalein-loaded β-cyclodextrin-grafted chitosan nanoparticles
Tang et al. Preparation, characterization, and Staphylococcus aureus biofilm elimination effect of baicalein-loaded tyrosine/hyaluronic acid/β-cyclodextrin-grafted chitosan nano-delivery system
CN1840184A (en) Lysozyme liposome and preparation method thereof
CN102885850B (en) Porous gel granules for treating vaginitis
Shipovskaya et al. Biocidal activity of chitosan aspartate nanoparticles

Legal Events

Date Code Title Description
PB01 Publication