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CN-121971407-A - Transferrin coating agent for relieving and treating Alzheimer's disease

CN121971407ACN 121971407 ACN121971407 ACN 121971407ACN-121971407-A

Abstract

The invention discloses a transferrin coating agent for relieving and treating Alzheimer's disease, which belongs to the technical field of biological medicines, and comprises transferrin-curcumin nanoparticles and a dispersion medium, wherein the transferrin-curcumin nanoparticles comprise curcumin and transferrin, the curcumin is directly coated in a hydrophobic cavity of the transferrin through hydrophobic interaction, and the dispersion medium is phosphate buffer solution containing ethanol in volume. The loading mode of the curcumin enables the hydrophobic curcumin to be coated in the hydrophilic carrier, thereby remarkably improving the water solubility and the stability in blood circulation, slowing down metabolic clearance, and simultaneously realizing high-efficiency and selective intracerebral delivery of the curcumin through a receptor-mediated endocytic transport mechanism by means of the specific combination of the transferrin and transferrin receptors on blood brain barrier endothelial cells.

Inventors

  • LI QING
  • GAO GUANGJIN

Assignees

  • 安徽农业大学
  • 诺海医康(苏州)生物技术有限公司

Dates

Publication Date
20260505
Application Date
20260319

Claims (10)

  1. 1. The transferrin coating agent is characterized by comprising transferrin-curcumin nanoparticles and a dispersion medium, wherein the transferrin-curcumin nanoparticles comprise curcumin and transferrin, the curcumin is directly coated in a hydrophobic cavity of the transferrin through hydrophobic interaction, and the dispersion medium is phosphate buffer solution containing ethanol in volume.
  2. 2. The transferrin coating agent of claim 1, wherein the molar concentration ratio of curcumin to transferrin is 6:1.
  3. 3. The transferrin-coating agent according to claim 1, wherein the transferrin-curcumin nanoparticle has a particle size of 18nm.
  4. 4. A method for preparing a transferrin coating agent according to any one of claims 1 to 3, comprising the steps of: Dissolving curcumin into ethanol solvent to obtain curcumin ethanol solution; dissolving transferrin in a phosphate buffer solution to obtain a transferrin solution; Under the mediation of ethanol, the curcumin ethanol solution is dripped into the mixed solution of the transferrin solution and the phosphate buffer solution, and under the conditions of whipping and ultrasonic vibration, the curcumin enters the hydrophobic cavity of the transferrin for self-assembly.
  5. 5. The method for producing a transferrin coating agent according to claim 4, wherein the concentration of the curcumin ethanol solution is 10mM, and the concentration of the transferrin solution is 1mM.
  6. 6. The method for producing a transferrin coating agent according to claim 4, wherein the transferrin coating agent has a volume content of ethanol of 1%.
  7. 7. The method for preparing a transferrin coating agent according to claim 4, wherein the dropping process is to add 5. Mu.l of the transferrin solution and 3. Mu.l of the curcumin ethanol solution to PBS solution to a volume of 500. Mu.l and an ethanol content of 1%.
  8. 8. The method of claim 4, wherein the duration of the whip and ultrasonic vibration is 20 minutes.
  9. 9. Use of a transferrin coating agent according to any one of claims 1 to 3 in the manufacture of a medicament for the alleviation or treatment of alzheimer's disease.
  10. 10. The use of claim 9, wherein the medicament is configured for administration by tail vein injection, and wherein curcumin is delivered into the brain by receptor-mediated endocytosis transport mechanism to inhibit brain neuroinflammation by specific binding of transferrin in the transferrin-coating agent to transferrin receptor on blood brain barrier endothelial cells.

Description

Transferrin coating agent for relieving and treating Alzheimer's disease Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a transferrin coating agent for relieving and treating Alzheimer's disease. Background Drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of AD mainly include two classes, acetylcholinesterase inhibitors (e.g., rivastigmine, galantamine) and NMDA receptor antagonists (memantine), but these drugs only temporarily relieve some of the symptoms and fail to alter the disease process. In recent years, the obtained Abeta targeting monoclonal antibodies (such as Aducanumab and Lecanemab) can clear Abeta in brain and delay clinical decline of early patients, and the curative effect is still limited. The first class of drugs (cholinesterase inhibitors and NMDA receptor antagonists) belongs to symptomatic treatment, and has the core disadvantage of failing to alter the underlying course of the disease, only temporarily improving the memory, thinking and behavioral symptoms of some patients, but failing to prevent the sustained degenerative changes of neurons in the brain and accumulation of pathological proteins. Its efficacy is generally limited and may decrease over time, with the potential for side effects such as gastrointestinal discomfort and dizziness. The bioavailability of oral curcumin is extremely low, it is difficult to be absorbed by the intestinal tract and is rapidly metabolized and cleared in the blood, resulting in systemic blood levels that are not always effective. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a transferrin coating agent for relieving and treating Alzheimer's disease, and solves the problems in the prior art. The aim of the invention can be achieved by the following technical scheme: The transferrin coating agent comprises transferrin-curcumin nanoparticles and a dispersion medium, wherein the transferrin-curcumin nanoparticles comprise curcumin and transferrin, the curcumin is directly coated in a hydrophobic cavity of the transferrin through hydrophobic interaction, and the dispersion medium is phosphate buffer solution containing ethanol in volume. Further, the molar concentration ratio of the curcumin to the transferrin is 6:1. Further, the particle size of the transferrin-curcumin nanoparticle is 18nm. The preparation method of the transferrin coating agent comprises the following steps: Dissolving curcumin into ethanol solvent to obtain curcumin ethanol solution; dissolving transferrin in a phosphate buffer solution to obtain a transferrin solution; Under the mediation of ethanol, the curcumin ethanol solution is dripped into the mixed solution of the transferrin solution and the phosphate buffer solution, and under the conditions of whipping and ultrasonic vibration, the curcumin enters the hydrophobic cavity of the transferrin for self-assembly. Further, the concentration of the curcumin ethanol solution is 10mM, and the concentration of the transferrin solution is 1mM. Further, in the transferrin coating agent, the volume content of ethanol is 1%. Further, the dropping process was such that 5. Mu.l of the transferrin solution and 3. Mu.l of the curcumin ethanol solution were added to PBS solution to a volume of 500. Mu.l and an ethanol content of 1%. Further, the duration of the whipping and ultrasonic oscillation is 20 minutes. The transferrin coating agent is applied to preparation of medicines for relieving or treating Alzheimer's disease. The drug is configured for administration by tail vein injection, and curcumin is delivered into the brain by a receptor-mediated endocytosis transport mechanism to inhibit brain neuroinflammation by utilizing the specific binding of transferrin in the transferrin-coating agent to transferrin receptors on blood brain barrier endothelial cells. The invention has the beneficial effects that: 1. The invention utilizes the hydrophobic cavity of Transferrin (TFR) to directly wrap fat-soluble curcumin molecules through hydrophobic interaction to form protein-drug complex, and the loading mode successfully coats hydrophobic curcumin with extremely poor water solubility in a hydrophilic transferrin carrier, thereby remarkably improving the water solubility of curcumin and the stability in blood circulation, effectively slowing down the metabolic clearance process of drugs in blood and overcoming the defect of extremely low bioavailability of oral curcumin. 2. According to the invention, the traditional organic solvents such as tetrahydrofuran, dimethyl sulfoxide and the like are abandoned, curcumin is firstly dissolved in ethanol, and is coated into PBS solution containing transferrin under the mediation of the ethanol, and the ethanol content of a final system is controlled to be 1%; the process successfully overcomes the technical bias that the traditional organic solvent can dissol