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CN-122005497-A - Tetrandrine and folic acid co-carried nanoparticle as well as preparation method and application thereof

CN122005497ACN 122005497 ACN122005497 ACN 122005497ACN-122005497-A

Abstract

The invention discloses a nanoparticle, which comprises tetrandrine, folic acid co-carried nano-liposome and a hyaluronidase layer coated on the surface of the co-carried nano-liposome. The invention also discloses a preparation method of the nanoparticle, which comprises the following steps of uniformly mixing tetrandrine, folic acid co-carried nano liposome aqueous dispersion liquid and hyaluronidase aqueous solution, carrying out electrostatic adsorption, and carrying out solid-liquid separation to obtain the nanoparticle. The invention also discloses nanoparticle freeze-dried powder, which comprises the nanoparticle and chitosan quaternary ammonium salt. The invention also discloses a preparation method of the nanoparticle freeze-dried powder. The invention also discloses the application of the nanoparticle and the nanoparticle freeze-dried powder in preparing medicaments for inhibiting and/or treating pulmonary fibrosis. The nanoparticle freeze-dried powder containing tetrandrine and folic acid has good effect of inhibiting pulmonary fibrosis.

Inventors

  • LI GUOYING
  • YANG GUANG
  • CHEN RU
  • LI YUTING
  • CHEN GUANGLIANG

Assignees

  • 安徽理工大学

Dates

Publication Date
20260512
Application Date
20260313

Claims (10)

  1. 1. The nanoparticle is characterized by comprising tetrandrine, folic acid co-carried nano-liposome and a hyaluronidase layer coated on the surface of the co-carried nano-liposome.
  2. 2. The nanoparticle of claim 1, wherein the content of tetrandrine in the co-loaded nanoliposome is 1-6wt% and the content of phylloic acid is 0.2-1.2wt%.
  3. 3. The nanoparticle according to claim 1 or 2, wherein the carrier of the tetrandrine and folic acid co-carried nano-liposome consists of lecithin, cationic lipid and cholesterol, wherein the cationic lipid is preferably at least one of (2, 3-dioleoxypropyl) trimethyl ammonium chloride, dioleoyl phosphatidylethanolamine and dioleoyl oxypropyl dimethyl ammonium chloride, the molar ratio of the lecithin, the cationic lipid and the cholesterol is preferably 1.5-2:1.5-2:1, and the tetrandrine and folic acid co-carried nano-liposome is preferably prepared by adopting a thin film dispersion method.
  4. 4. A nanoparticle according to any one of claims 1 to 3, wherein the co-entrapped nanoliposomes are coated with the hyaluronidase layer by electrostatic interaction, preferably the nanoparticle has a particle size of 100 to 300nm.
  5. 5. A method for preparing nanoparticles according to any one of claims 1 to 4, comprising the steps of uniformly mixing tetrandrine, folic acid co-carried nano liposome aqueous dispersion and hyaluronidase aqueous solution, carrying out electrostatic adsorption, and carrying out solid-liquid separation to obtain the nanoparticles.
  6. 6. The method for preparing nanoparticles according to claim 5, wherein the mass fraction of the aqueous hyaluronidase solution is 0.05-0.15wt%, preferably the mass fraction of the tetrandrine and folic acid co-supported nanoliposome is 2-3wt%, preferably the volume ratio of the tetrandrine, folic acid co-supported nanoliposome aqueous dispersion to the hyaluronidase solution is 1:0.8-1, and preferably the tetrandrine and folic acid co-supported nanoliposome aqueous dispersion is electrostatically adsorbed at room temperature for 0.5-1h.
  7. 7. A nanoparticle lyophilized powder comprising the nanoparticle according to any one of claims 1 to 4 and chitosan quaternary ammonium salt.
  8. 8. The nanoparticle lyophilized powder of claim 7, wherein the weight ratio of nanoparticle to chitosan quaternary ammonium salt is 1:0.8-1.2, preferably the chitosan quaternary ammonium salt is N- (2-hydroxy) propyl-3-methyl ammonium chloride chitosan.
  9. 9. A method for preparing the nanoparticle lyophilized powder according to claim 7 or 8, comprising the steps of dispersing the nanoparticle in water, adding chitosan quaternary ammonium salt, mixing, electrostatic adsorbing, and lyophilizing to obtain the nanoparticle lyophilized powder.
  10. 10. Use of a nanoparticle according to any one of claims 1 to 4, a nanoparticle lyophilized powder according to claim 7 or 8, for the manufacture of a medicament for inhibiting and/or treating pulmonary fibrosis, preferably pulmonary fibrosis to pneumoconiosis.

Description

Tetrandrine and folic acid co-carried nanoparticle as well as preparation method and application thereof Technical Field The invention relates to the technical field of pulmonary fibrosis treatment, in particular to tetrandrine and folic acid co-supported nano-particles, and a preparation method and application thereof. Background Pneumoconiosis is a disease caused by long-term inhalation of inorganic mineral dust and characterized by diffuse nodular or latticed fibrosis of the lung tissue. The etiology is often due to occupational or environmental factors such as silica dust, asbestos dust, or carbon black dust, among others. Pneumoconiosis is classified into many types, such as silicosis, coal dust, graphite dust, asbestosis, and the like. The onset factors are related to the particle size of the dust, the concentration of the dust, the contact time and the like. In the early stage, the patient may have no obvious symptoms, but with the progress of the disease, the main symptoms are cough, expectoration, shortness of breath and the like. Complications include tuberculosis, pulmonary heart disease, acute respiratory failure, and the like. The main treatment methods of pneumoconiosis include symptomatic treatment, drug treatment, separation from dust working environment and the like. Pulmonary function rehabilitation is of great benefit for alleviating symptoms and improving quality of life. Patients with end-stage pneumoconiosis may need to receive lung transplants. Tetrandrine clearly delays the effect of pneumoconiosis fibrosis, but the effect of tetrandrine singly needs to be improved, and the tetrandrine is prepared into tablets or injections at present, and cannot directly act on the lung to influence the drug effect. Disclosure of Invention Based on the technical problems in the background technology, the invention provides tetrandrine and folic acid co-carried nano-particles, and a preparation method and application thereof. The invention provides a nanoparticle, which comprises tetrandrine, folic acid co-carried nano-liposome and a hyaluronidase layer coated on the surface of the co-carried nano-liposome. Preferably, the content of tetrandrine in the co-carried nano liposome is 1-6wt% and the content of phylloic acid is 0.2-1.2wt%. Preferably, the carrier of the tetrandrine and folic acid co-carried nano liposome consists of lecithin, cationic lipid and cholesterol. Preferably, the cationic lipid is at least one of (2, 3-dioleoxypropyl) trimethylammonium chloride, dioleoyl phosphatidylethanolamine, dioleoyloxypropyl dimethylammonium chloride. Preferably, the molar ratio of lecithin, cationic lipid, cholesterol is 1.5-2:1.5-2:1. Preferably, the tetrandrine and folic acid co-carried nano liposome is prepared by adopting a film dispersion method. The film dispersing process includes dissolving tetrandrine, lecithin, cationic lipid and cholesterol in organic solvent, evaporating to form film, adding folic acid buffering water solution for hydration to obtain suspension, ultrasonic treatment, homogenizing to form film, and dialyzing with water to obtain tetrandrine-folic acid carried nanometer liposome water dispersion. The tetrandrine and folic acid co-carried nano liposome can be stored in a solution form for standby. The weight ratio of the lecithin, the cationic lipid and the cholesterol to the tetrandrine is 17-53:1. The organic solvent may be ethanol, chloroform, etc., and the lecithin may be soybean lecithin, etc. The above evaporation is reduced pressure rotary evaporation ‌, the evaporation temperature is preferably ‌ -45deg.C ‌, the evaporation rotation speed is preferably 80-120rpm, and the evaporation time is preferably 2-4 hr. ‌ The above folic acid buffer aqueous solution is ‌ phosphate buffer, preferably pH 7.3-7.5. The dosage ratio of the folic acid buffer aqueous solution to the lecithin is preferably 10ml to 0.75-1.5mmol. The hydration temperature is preferably 40-45deg.C, and the hydration time is preferably 1-1.5 hr. The stirring speed is preferably 300-500 rpm while hydrating, and the ‌ ultrasonic time is preferably 10-20min. ‌ The molecular cut-off of the dialysis bag is 3500, the dialysis time is 8-12h, and water is changed every 4h. Preferably, the encapsulation is achieved by electrostatic interaction of the nanoliposome and the hyaluronidase layer. Preferably, the particle size of the nanoparticles is 100-300nm. The invention also provides a preparation method of the nanoparticle, which comprises the following steps of uniformly mixing tetrandrine, folic acid co-carried nano liposome aqueous dispersion liquid and hyaluronidase aqueous solution, carrying out electrostatic adsorption, and carrying out solid-liquid separation to obtain the nanoparticle. Preferably, the aqueous hyaluronidase solution has a mass fraction of 0.05-0.15wt%. Preferably, the mass fraction of the tetrandrine and folic acid co-carried nano-liposome in the tetrandrine and folic acid co-carried nano-liposome