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CN-122005489-A - FACOD@DSPE nano particle, preparation method and application thereof in antibiosis/sterilization

CN122005489ACN 122005489 ACN122005489 ACN 122005489ACN-122005489-A

Abstract

The invention relates to the technical field of biological preparation, in particular to FACOD@DSPE nano particles, a preparation method and application thereof in animal antibiosis/sterilization, wherein the preparation method comprises the steps of (1) mixing and stirring a compound IV and a compound COD, then adding N, N-diisopropylethylamine at room temperature overnight, extracting by a separating funnel, drying, filtering, separating and purifying to obtain FACOD; and (2) wrapping the FACOD with distearoyl phosphatidylethanolamine-methoxy polyethylene glycol to construct the FACOD@DSPE nanoparticles. Compared with the prior art, the FACOD@DSPE nano particles with the light response characteristic can be cooperatively released under the illumination condition, the yield of FA is about 85.02%, the yield of CO is 50.3%, the sterilization rate of Escherichia coli is 91.36-99.80%, the sterilization rate of staphylococcus aureus is 94.11-99.85%, the sterilization rate of drug-resistant staphylococcus aureus is 86.83-98.92%, and the FACOD@DSPE nano particles have the characteristics of low toxicity to cells and mice and good biosafety.

Inventors

  • YANG LEI
  • LIN ZHENMEI
  • LI LI
  • CHEN SONGLIN
  • LI SHENG
  • ZHANG KEXING
  • TAN LING
  • ZHU KEYING

Assignees

  • 广西中医药大学第一附属医院(广西中医医院)

Dates

Publication Date
20260512
Application Date
20260120

Claims (10)

  1. 1. A preparation method of FACOD@DSPE nano particles, the preparation method is characterized by comprising the following steps: (1) Mixing compound IV and compound COD, adding N, N-diisopropylethylamine, stirring at room temperature overnight, extracting with a separating funnel, drying, filtering, separating and purifying to obtain FACOD; (2) And wrapping FACOD by using distearoyl phosphatidylethanolamine-methoxy polyethylene glycol to construct the FACOD@DSPE nano particles.
  2. 2. The method for preparing the FACOD@DSPE nanoparticles according to claim 1, wherein the method for preparing the compound COD is as follows: Adding sodium hydroxide aqueous solution into a compound III, stirring at room temperature for 30 minutes to obtain a first reaction mixture, adding benzaldehyde into the first reaction mixture, stirring at room temperature for 5 hours to obtain a second reaction mixture, cooling the second reaction mixture to 0 ℃ in an ice bath, adding K 2 O 2 , heating to room temperature, stirring overnight, acidifying the solution with hydrochloric acid, filtering to obtain a precipitate, and washing the precipitate with ethanol to obtain a compound COD.
  3. 3. The method for preparing FACOD@DSPE nanoparticles according to claim 2, The chemical formula of the compound III is as follows: ; The chemical formula of the compound COD is as follows: The chemical name of the chemical compound COD is 7-hydroxy-4-phenyl-3H-naphtho [2,3-c ] furan-1-one.
  4. 4. The method for preparing the FACOD@DSPE nanoparticles according to claim 1, wherein the preparation method of the compound IV is as follows: (1) Adding a compound I into anhydrous acetonitrile, mixing and cooling to 0 ℃, adding dimethyl sulfide, charging nitrogen for protection, adding benzoyl peroxide, reacting for 6 hours at 0 ℃, adjusting the pH to 9, reacting overnight, extracting, drying, filtering, taking filtrate, evaporating to dryness in a rotary manner, and purifying to obtain a compound II; (2) And adding the compound II into anhydrous dichloromethane, cooling to 0 ℃, slowly adding sulfonyl chloride, continuing to react for 8 hours under the room temperature condition by utilizing nitrogen protection, extracting to obtain an organic phase, drying, filtering to obtain a filtrate, and then evaporating to dryness in a rotary manner, and separating and purifying to obtain the compound IV.
  5. 5. The method for preparing FACOD@DSPE nanoparticles according to claim 4, The chemical formula of the compound I is as follows: the name of the compound I is 2 nitryl Chun; the chemical formula of the compound II is as follows: , the chemical formula of the compound IV is as follows: the chemical name of the compound IV is 2-nitrobenzyloxy chloromethane.
  6. 6. The facod@dspe nanoparticle prepared by the preparation method of the facod@dspe nanoparticle according to any one of claims 1 to 5, wherein FACOD in the facod@dspe nanoparticle has a structural formula as follows: 。
  7. 7. use of the facod@dspe nanoparticle according to any one of claims 1-6 for the preparation of an animal light responsive antibacterial or/and bactericidal formulation.
  8. 8. The use of the facod@dspe nanoparticle according to claim 7 for the preparation of an animal light responsive antibacterial or/and bactericidal formulation, wherein the antibacterial or bactericidal species is a drug resistant staphylococcus aureus.
  9. 9. The use of the facod@dspe nanoparticle according to claim 7 for the preparation of an animal light responsive antibacterial or/and bactericidal formulation, wherein the antibacterial or bactericidal species is staphylococcus aureus.
  10. 10. A formulation comprising the facod@dspe nanoparticle according to any one of claims 1 to 6 in a concentration of 30 to 50 μm, wherein the formulation is an animal light responsive antibacterial or/and bactericidal formulation and the species killed or/and inhibited by the formulation is escherichia coli or/and drug resistant staphylococcus aureus or/and staphylococcus aureus.

Description

FACOD@DSPE nano particle, preparation method and application thereof in antibiosis/sterilization Technical Field The invention relates to the technical field of biological preparation, in particular to FACOD@DSPE nano particles, a preparation method and application thereof in antibiosis. Background Gas therapy is an emerging disease intervention strategy, gas therapy mainly comprises Nitric Oxide (NO), CO and hydrogen sulfide (H 2 S), wherein the gas molecules are controlled through key signal channels in pathological microenvironment, the gas has been proved to respectively realize the effects of inhibiting neutrophil infiltration, relieving ischemia reperfusion injury, antagonizing oxidative stress and the like through controlling sGC/cGMP, HO-1, nrf2/KEAP1 and the like, the gas therapy has important progress in inflammatory disease therapy, and in recent years, the gas therapy has great potential in the field of important disease therapy, and typical examples comprise Nitric Oxide (NO), hydrogen sulfide (H 2 S), oxygen (O 2), carbon monoxide (CO) and Formaldehyde (FA). Compared with traditional chemical medicine treatment, the gas treatment has obvious advantages. First, the gas molecules do not develop resistance during treatment and enhance the sensitivity of the resistant cells to chemotherapeutic drugs 3. Second, the gas involved in this approach is mostly an important endogenous signal molecule in the organism, playing a vital role in various biological processes, and thus gas therapy is considered as a highly biocompatible therapeutic strategy 4. Whichever gas is difficult to be used directly as a treatment due to its reactivity, dispersibility, etc. Gas therapy therefore requires the use of their donors, capable of releasing gas in situ, to achieve therapeutic effects. In recent years, a class of flavonol (Flavnol) compounds can release CO 2 and generate a gradually weakened fluorescence signal under light irradiation, and hydroxyl groups on flavonols have modifiable property and can be used as linking points of gas release groups, so that the flavonol compounds are a potential double-gas-donor development platform. Therefore, the double-gas molecular donor is developed based on the flavonol compound, the gas is released in a controllable mode, and a fluorescent signal is generated in situ, so that the gas release process is in a visible state, a novel technical means is provided for double-gas combined treatment, and an important molecular tool is provided for researching a combined action mechanism of the double gases. Disclosure of Invention The invention aims to provide FACOD@DSPE nano particles, a preparation method and application thereof in antibiosis/sterilization, and aims to prepare a novel compound capable of cooperatively releasing formaldehyde and carbon monoxide under illumination condition by adopting a novel preparation method. In order to achieve the above object, the present invention provides a preparation method of facod@dspe nanoparticles, the preparation method comprising: (1) 314.68mg of compound IV and 300 mg COD are mixed, dichloromethane is used as a solvent for dissolution, 268.98mg of N, N-diisopropylethylamine is added for uniform mixing, mixing and stirring are carried out at room temperature overnight, extraction is carried out by a separating funnel, drying, filtering, separation and purification are carried out, and FACOD is obtained; (2) 3.07 mg of FACOD is weighed and dissolved in CHCl 3 to prepare FACOD (CHCl 3) solution, FACOD (CHCl 3) solution is added into 1 mg/mL distearoyl phosphatidyl ethanolamine-methoxy polyethylene glycol solution drop by drop, DSPE-PEG2000 is fully wrapped with FACOD, chloroform is removed, and FACOD@DSPE nano particles are obtained. Preferably, in the above technical scheme, the preparation method of the compound COD is as follows: 3.90g of compound III is weighed, 60mL of ethanol solution is added for dissolution, 21mL of sodium hydroxide aqueous solution is added to the compound III solution, stirring is carried out at room temperature for 30 minutes to obtain a first reaction mixture, 2.14mL of benzaldehyde is added to the first reaction mixture, stirring is carried out at room temperature for 5 hours to obtain a second reaction mixture, 4.6g K 2O2 is added after the second reaction mixture is cooled to 0 ℃ in an ice bath, stirring is carried out at room temperature for overnight, the solution is acidified to pH=6.5 by hydrochloric acid, a precipitate is filtered, and the precipitate is washed with 3x10mL of ethanol to obtain compound COD. Preferably, in the above technical scheme, the chemical formula of the compound III is as follows: the chemical formula of the compound COD is as follows: The chemical name of the chemical compound COD is 7-hydroxy-4-phenyl-3H-naphtho [2,3-c ] furan-1-one. Preferably, in the above technical scheme, the preparation method of the compound IV is as follows: (1) Adding 1.5g of compound I into 50mL o