CN-122005588-A - Pharmaceutical composition containing evodiaoside, drug carrying system and application thereof in osteoarthritis

Abstract

The invention discloses a medicinal composition containing evodiaoside, a medicine carrying system and application thereof in osteoarthritis, and belongs to the technical field of biological medicines. The invention discovers that the evodiamine can obviously inhibit the apoptosis of the chondrocytes and promote the proliferation of the chondrocytes for the first time, and provides a brand new candidate compound for the treatment of osteoarthritis. In order to further improve the curative effect, the invention designs a medicinal composition which can interfere macrophage polarization or regulate joint inflammation microenvironment and can simultaneously act on two key pathological links of cartilage repair and inflammation regulation, and the curative effect of osteoarthritis is greatly improved through a synergistic effect.

Inventors

• QU DING
• ZHANG ZHENZHEN
• ZHOU JING
• GUO JUN

Assignees

• 江苏省中医药研究院(江苏省中西医结合医院)

Dates

Publication Date

20260512

Application Date

20260203

Claims (9)

1. 1. Application of evodiaoside in preparing medicine for preventing and/or treating osteoarthritis is provided.
2. 2. A pharmaceutical composition is characterized by comprising a therapeutically effective amount of evodiaoside and a therapeutically effective amount of at least one second active agent, wherein the second active agent is a medicament with the function of interfering macrophage polarization or regulating joint inflammation microenvironment.
3. 3. The pharmaceutical composition of claim 2, wherein the second active agent is selected from the group consisting of celastrol, lupeol, ginsenoside Rg1, ursolic acid, curcumin, puerarin, leonurine, anti-GM-CSF antibodies.
4. 4. The bionic drug carrying system is characterized by comprising an active ingredient, a drug carrier and a cell membrane, wherein the drug carrier carries the active ingredient, and the cell membrane is coated outside the drug carrier; The active ingredient is the pharmaceutical composition of claim 2 or 3; The drug carrier is selected from mesoporous cerium oxide nano carrier, mesoporous silicon, liposome and polylactic acid-glycolic acid copolymer; the cell membrane is selected from macrophage membrane, cartilage cell membrane, erythrocyte membrane and neutrophil granulocyte membrane.
5. 5. The biomimetic drug delivery system of claim 4, wherein the drug carrier is a mesoporous cerium oxide nano carrier and the cell membrane is a macrophage.
6. 6. The method for preparing the bionic drug delivery system according to claim 4, comprising the steps of: Step 1, dispersing a drug carrier and an active ingredient in a solvent together to obtain a drug-carrier compound, and centrifuging and drying to obtain drug-carrying nanoparticles; And 2, dispersing the drug-carrying nanoparticles and the cell membrane in a water phase, and performing ultrasonic treatment to obtain the bionic drug-carrying system.
7. 7. The preparation method of claim 6, wherein in the step 1, the feeding mass ratio of the drug carrier, the evodiamine and the second active ingredient is (80-320): 20-40): 4-120.
8. 8. The preparation method of claim 6, wherein in the step 2, the mass ratio of the cell membrane to the drug-loaded nanoparticle is (1-4): 1-2.
9. 9. Use of a pharmaceutical composition according to claims 2-3 or a biomimetic drug delivery system according to claims 4-5 for the manufacture of a medicament for the prevention and/or treatment of osteoarthritis.

Description

Pharmaceutical composition containing evodiaoside, drug carrying system and application thereof in osteoarthritis Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a medicinal composition containing evodiaoside, a medicine carrying system and application of the medicinal composition in osteoarthritis. Background Osteoarthritis is a chronic degenerative disease with progressive destruction of articular cartilage as a core, and current clinical therapeutic drugs (such as non-steroidal anti-inflammatory drugs, glucocorticoids, etc.) can only relieve symptoms, but cannot delay or reverse the pathological process. In the complex pathological network of osteoarthritis, excessive apoptosis of chondrocytes is a key element driving cartilage degradation. In one aspect, apoptotic chondrocytes release large amounts of Reactive Oxygen Species (ROS), up-regulate focal oxidative stress levels, impair mitochondrial function and interfere with mitochondrial autophagy, resulting in impaired mitochondrial accumulation, further exacerbating apoptosis. On the other hand, the joint cavity inflammation microenvironment leads macrophages to M1 type polarization, releases a large amount of pro-inflammatory factors such as TNF-alpha, IL-1 beta and the like, further stimulates the apoptosis of chondrocytes, forms pathological circulation of 'oxidative stress-apoptosis-inflammation' interweaving with each other and continuously amplifying, and continuously promotes the disease progress. Therefore, a novel therapeutic strategy capable of simultaneously enhancing the oxidation resistance of chondrocytes, inhibiting the apoptosis of the chondrocytes and inhibiting the inflammation is developed, and has important significance for breaking the vicious circle and fundamentally interfering with the pathological process of osteoarthritis. Finding an osteoarthritis treatment drug in natural products is an important direction. The prior art (CN 114344319 a) discloses that evodia rutaecarpa glycoside is used for treating rheumatoid arthritis by promoting apoptosis of fibroblast-like synovial cells, but there is a fundamental difference in pathological mechanism between rheumatoid arthritis (autoimmune disease, synovial cells requiring inhibition of abnormal proliferation) and osteoarthritis (degenerative disease, chondrocytes requiring protection from apoptosis). The "pro-apoptotic" mechanism relied on by this prior art, in contrast to the therapeutic need for osteoarthritis to inhibit chondrocyte apoptosis, does not provide any beneficial insight, but rather prevents those skilled in the art from using evodiamine for the treatment of osteoarthritis. The invention discovers for the first time that evodiaoside shows a novel function which is completely opposite to the cognition of the prior art in the osteoarthritis environment, namely, obviously inhibits the apoptosis of chondrocytes and promotes the proliferation of the chondrocytes. The novel pharmacological activity provides novel candidate compounds for the treatment of osteoarthritis. In order to further improve the curative effect, the inventor designs a medicinal composition which can interfere macrophage polarization (such as rambutan red and the like) or regulate joint inflammation microenvironment and can simultaneously act on two key pathological links of cartilage repair and inflammation regulation, and the curative effect of osteoarthritis is greatly improved through a synergistic effect. However, delivering an effective drug combination to the site of an osteoarthritis focus and achieving precise release presents a significant challenge. For example, the medicines such as tripterine have the problems of poor water solubility, high toxicity and the like, while the joint cavity environment of osteoarthritis is complex, and the conventional medicine carrying system has the defects of insufficient targeting, lack of focus microenvironment responsiveness, incapability of controlling medicine release and the like, so that the effective medicine concentration and proportion are difficult to maintain at focus positions. Therefore, a novel drug delivery system which can effectively carry evodiaoside and a combination drug thereof, realize focus targeted aggregation and respond to the osteoarthritis microenvironment to control drug delivery as required is urgently needed. The development of a delivery platform integrating the functions is a key technical path for realizing pharmaceutical application of evodiaoside and the composition thereof and breaking through the bottleneck of the current osteoarthritis treatment. Disclosure of Invention The invention aims at providing an application of evodiaoside in preparation of a medicament for preventing and/or treating osteoarthritis. The invention discloses a new medical application of evodiaoside in the treatment of osteoarthritis for the first time. In particular, it was found and