CN-121287925-B - Brain-targeted nano preparation for treating depression and preparation method and application thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine research and development, and particularly provides a brain-targeted nano preparation for treating depression, and a preparation method and application thereof. The preparation takes graphene oxide, polyethylene glycol, acteoside and ferulic acid as raw materials, and realizes multicomponent synergistic brain targeting drug delivery by constructing a nano co-delivery carrier. Firstly, performing functional modification on graphene oxide by using polyethylene glycol, then grafting ferulic acid on the surface of a modified carrier, and finally loading verbascoside to form the composite nano preparation. The design fully plays the brain targeting function of ferulic acid and the antidepressant effect of the acteoside, synergistically enhances the curative effect, reduces the drug resistance and adverse reaction, and realizes multi-component intra-brain directional co-delivery.

Inventors

• MA KE
• Huang Liuxuan
• ZHANG HONGXIU
• Tian Haoquan
• YANG WENGUANG
• FANG XINYU
• YE HAN

Assignees

• 山东中医药大学

Dates

Publication Date

20260505

Application Date

20251105

Claims (7)

1. 1. The preparation method of the traditional Chinese medicine multi-component brain-targeting nano preparation for treating depression is characterized by comprising the following steps: (1) Preparing blank nano-carrier PEG-GO: adding polyethylene glycol PEG into the graphene oxide GO dispersion liquid, uniformly mixing and performing ultrasonic treatment; Then EDC is added for reaction, dialysis and purification are carried out, and PEG-GO freeze-dried powder is obtained through freeze drying; (2) Preparing a single-component nano drug-loaded preparation PEG-GO-FA loaded with ferulic acid FA: dispersing PEG-GO freeze-dried powder in water, adding FA according to the mass ratio of FA to PEG-GO of 1:10, performing ultrasonic treatment, stirring for reaction, dialyzing for purification, and freeze-drying to obtain PEG-GO-FA freeze-dried powder; (3) Preparing a multi-component nano drug-carrying preparation ACT-PEG-GO-FA loaded with acteoside and ferulic acid FA: Dispersing PEG-GO-FA freeze-dried powder in water, adding ACT according to the mass ratio of ACT to PEG-GO-FA of 1:10, carrying out ultrasonic treatment, stirring for reaction, dialyzing for purification, and freeze-drying to obtain the ACT-PEG-GO-FA solid nano preparation.
2. 2. The method according to claim 1, wherein in the step (1), the concentration of the graphene oxide dispersion is 1 mg/mL, the polyethylene glycol is added in an amount 10 times by mass of the volume of the graphene oxide dispersion, and the time of the ultrasonic treatment is 5 min; the EDC is added to react, namely the EDC is firstly added to lead the final concentration to be 5mM, the ultrasonic treatment is continued for 30min, then the EDC is added to lead the final concentration to be 20mM, and the reaction condition is that the reaction is carried out at room temperature for 12 h; The molecular weight cut-off of the dialysis purification was 10 kDa and the time of the dialysis purification was 48 h.
3. 3. The method according to claim 2, wherein in the step (2), the time of the ultrasonic treatment is 30min, the time of the stirring reaction is 24 h, the molecular weight cut-off of the dialysis purification is 3.5 kDa, and the time of the dialysis purification is 24 h.
4. 4. The method according to claim 3, wherein in the step (3), the time of the ultrasonic treatment is 30min, the time of the stirring reaction is 24 h, the molecular weight cut-off of the dialysis purification is 3.5 kDa, and the time of the dialysis purification is 24 h.
5. 5. The Chinese medicine multicomponent brain targeting nano preparation for treating depression is characterized by comprising the following raw materials: Nano-carrier PEG-GO, ferulic acid and acteoside; the mass ratio of the nano carrier PEG-GO to the ferulic acid to the acteoside is 10:1:1; The traditional Chinese medicine multi-component brain-targeting nano preparation is prepared by the preparation method of any one of claims 1-4.
6. 6. Use of the multi-component brain-targeted nano-formulation of traditional Chinese medicine according to claim 5 in the preparation of a medicament for treating depression.
7. 7. A pharmaceutical composition for treating depression, which is characterized by comprising the traditional Chinese medicine multi-component brain-targeting nano-preparation of claim 5 and pharmaceutically acceptable auxiliary materials; In the pharmaceutical composition, the mass content of the traditional Chinese medicine multi-component brain-targeting nano preparation is more than or equal to 8.06%; The administration mode of the pharmaceutical composition is intravenous injection.

Description

Brain-targeted nano preparation for treating depression and preparation method and application thereof Technical Field The invention belongs to the technical field of traditional Chinese medicine research and development, and particularly provides a brain-targeted nano preparation for treating depression, and a preparation method and application thereof. Background Depression is a common mental disorder, about 3.5 hundred million patients worldwide, and the symptoms of continuous mood depression, loss of pleasure, sleep disorder, psychomotor retardation, cognitive function impairment and the like seriously impair physical and mental health and social functions of the patients, and bring about heavy social burden. The disease not only increases the economic pressure of families and medical treatment significantly, but also is one of the main reasons for the loss of working capacity, and has become a serious public health problem which needs to be dealt with in the global scope. In modern medicine, clinical first-line drug treatment of depression mainly includes selective 5-hydroxytryptamine reuptake inhibitors (SSRIs, such as fluoxetine, paroxetine, sertraline), 5-hydroxytryptamine and norepinephrine reuptake inhibitors (SNRIs, such as venlafaxine, duloxetine), norepinephrine and specific 5-hydroxytryptamine antidepressants (NaSSA, such as mirtazapine), and other classes of drugs (such as bupropion). Although these drugs are widely used in clinic and have a certain therapeutic effect, their limitations are also very prominent. Common adverse effects include central nervous system symptoms (such as insomnia, dizziness, somnolence, tremor), gastrointestinal discomfort (nausea, vomiting, diarrhea or constipation), autonomic dysfunction (hyperhidrosis, palpitations), sexual dysfunction, weight changes, and the like. In addition, some patients have a slow therapeutic response, incomplete relief of symptoms, and even interruption of treatment due to drug resistance or intolerance of side effects, severely affecting medication compliance and long-term prognosis. In recent years, various traditional Chinese medicine monomer components have obvious potential in antidepressant mechanism research. For example, ginsenoside Rg1 relieves depression-like behavior through neuroprotection, resveratrol improves depression by anti-inflammatory, neurotransmitter regulation and HPA axis overactivation inhibition, paeoniflorin reverses reserpine-induced depression behavior, promotes hippocampal dendritic spine generation and inhibits neuroinflammatory response. The components not only have the action characteristics of multiple targets and multiple ways, but also show unique therapeutic advantages. However, they generally face pharmaceutical bottlenecks such as low water solubility, poor bioavailability, difficulty in penetrating the blood brain barrier and the like, and severely restrict the clinical transformation and practical application thereof. Meanwhile, the existing chemical antidepressant drugs also have obvious limitations, such as long treatment course, high recurrence rate, potential dependence risk and obvious side effects. Under the background, development of novel drug delivery formulations to improve therapeutic effects and reduce adverse reactions has become an urgent and daily direction in antidepressant therapy research. Disclosure of Invention The invention aims to provide a brain-targeted nano preparation for treating depression, and a preparation method and application thereof, thereby developing a novel anti-depression therapeutic drug. In order to achieve the above purpose, the present invention provides the following technical solutions: Firstly, the invention provides a preparation method of a traditional Chinese medicine multi-component brain-targeting nano preparation for treating depression, which comprises the following steps: (1) Preparing blank nano-carrier PEG-GO: adding polyethylene glycol (PEG) into Graphene Oxide (GO) dispersion liquid, uniformly mixing, and performing ultrasonic treatment; Then EDC is added for reaction, dialysis and purification are carried out, and PEG-GO freeze-dried powder is obtained through freeze drying; (2) Preparing a single-component nano drug-loaded preparation PEG-GO-FA loaded with ferulic acid FA: dispersing PEG-GO freeze-dried powder in water, adding FA according to the mass ratio of FA to PEG-GO of 1:10, performing ultrasonic treatment, stirring for reaction, dialyzing for purification, and freeze-drying to obtain PEG-GO-FA freeze-dried powder; (3) Preparing a multi-component nano drug-carrying preparation ACT-PEG-GO-FA loaded with acteoside and ferulic acid FA: Dispersing PEG-GO-FA freeze-dried powder in water, adding ACT according to the mass ratio of ACT to PEG-GO-FA of 1:10, carrying out ultrasonic treatment, stirring for reaction, dialyzing for purification, and freeze-drying to obtain the ACT-PEG-GO-FA solid nano preparation. Preferably, in the step (1), t