Targeting liposome for treating rheumatoid arthritis and preparation method thereof

A technology of targeting liposomes and targeting ligands, which is applied in liposome delivery, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem that the anti-RA effect has not been obtained clinically. Fully exert, short pharmacokinetic half-life, serious systemic side effects and other problems, to achieve the effect of improving accuracy, increasing cycle time, and protecting cartilage tissue

Pending Publication Date: 2021-12-21
LIAONING UNIV OF TRADITIONAL CHINESE MEDICINE
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, TP has poor solubility, serious systemic side effects, and short pharmacok

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Targeting liposome for treating rheumatoid arthritis and preparation method thereof
  • Targeting liposome for treating rheumatoid arthritis and preparation method thereof
  • Targeting liposome for treating rheumatoid arthritis and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 Preparation of liposomes.

[0050] 1. Targeting ligand DSPE-PEG 2000 - Preparation of FA.

[0051] Dissolve FA, dicyclohexylcarbodiimide (DCC) and NHS in the ratio of (0.2-2):(0.5-4):(0.2-3) in dimethyl sulfoxide (DMSO) . Act at 15°C-50°C for 2h-6h, and then centrifuge twice. The supernatant was quickly transferred to a centrifuge tube with anhydrous ether and acetone (7:3, v / v) at 0°C-10°C, and centrifuged to obtain a yellow solid. The preliminary product was washed twice and dried overnight to obtain FA-NHS. FA-NHS, DSPE-PEG-NH 2 , Pyridine dissolved in DMSO at room temperature, FA-NHS and DSPE-PEG-NH 2 The ratio of the amount of substances is (1-3): (0.3-3), the reaction temperature is 15°C-50°C, and the reaction time is 10h-48h. The reaction product was placed under vacuum at 60° C. using a diaphragm pump to remove pyridine. The resulting mixture was dialyzed against distilled water (25,000 Da cut-off) for 48 hours to finally obtain DSPE-PEG-FA.

...

Embodiment 2

[0060] Example 2 In vitro targeting studies of liposomes.

[0061] 1 Cell culture.

[0062] Mouse mononuclear macrophage leukemia cells RAW264.7 cells were cultured in DMEM medium (containing 10% fetal bovine serum and 5% 100 U / mL penicillin and 100 μg / mL streptomycin), at 37 ℃ and containing 5% CO 2 cultured in a constant temperature cell incubator. According to the specific cell number and growth state in the culture flask, the RAW264.7 cells in the logarithmic growth phase were used for the experiment.

[0063] 2 Cytotoxicity.

[0064] 2.1 The SRB method was used to determine the survival rate of RAW264.7 cells in vitro.

[0065] Take RAW264.7 cells in the logarithmic growth phase in 5×10 3 The concentration of cells per well The cells were seeded in a 96-well plate, and four parallel wells were set up for different dosage concentrations. Continue to incubate for 24 h, and add different concentrations of free drugs and liposomes to each well. After incubation for 48 ...

Embodiment 3

[0077] Example 3 In vivo pharmacodynamic study of liposomes.

[0078] 1. Establishment of CIA model rats.

[0079] Dissolve chicken type II collagen in freshly prepared acetic acid solution and stir overnight at 4°C. The next day, add the collagen solution dropwise to Freund's complete adjuvant on ice, stir for about 2 hours, emulsify it completely, and use it as the primary immunization; the preparation method of the secondary immune agent is the same as above, just add the collagen solution to Freund's Incomplete adjuvants are sufficient. Inject 100 μL of primary immunization agent subcutaneously at the root of each rat's tail, and continue to inject secondary immunization agent to boost immunization 7 days later. If severe swelling occurs in the joints of the rats, the modeling is considered successful.

[0080] 2. The tissue distribution of liposomes in the living state of CIA rats.

[0081] The optical imaging system is used for observation, and the fluorescent probe i...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Apertureaaaaaaaaaa
Particle sizeaaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a triptolide targeting liposome for treating rheumatoid arthritis and a preparation method thereof. The long-circulating targeting liposome is composed of triptolide, a membrane material and a targeting ligand. According to the triptolide long-circulating targeting liposome and the preparation method thereof provided by the invention, the liposome is modified by DSPE-PEG2000 and DSPE-PEG2000-FA to obtain a brand new targeting liposome, and the targeting liposome can enable a drug to target an inflammation part; the triptolide is encapsulated in a hydrophobic bilayer of a biological membrane-like film, thereby better exerting the effects of immunosuppression, inflammation resistance and cartilage tissue protection. The invention provides a new countermeasure for treatment of the rheumatoid arthritis, and has important theoretical significance and clinical significance.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a triptolide-targeted liposome for treating rheumatoid arthritis and a preparation method thereof. Background technique [0002] Rheumatoid arthritis (RA) is an autoimmune disease involving joints, and its incidence accounts for nearly 1% of the total population. RA is widely distributed around the world and can occur at any age. The number of female patients is 2-3 times that of male patients. RA belongs to the "disadvantage syndrome" in traditional Chinese medicine. It is characterized by erosion and damage of articular cartilage, synoviocyte hyperplasia and bone destruction. The main clinical feature of the disease is erosive and symmetrical arthritis. Involvement of the knee, ankle, and foot joints is most common. The pathogenesis of RA is also prone to complications such as cardiovascular disease, respiratory system disease, and renal insufficiency. ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K9/127A61K31/585A61K47/24A61K47/28A61K47/54A61P19/02A61P29/00
CPCA61K9/1277A61K9/1271A61K31/585A61K47/545A61K47/24A61K47/28A61P19/02A61P29/00Y02A50/30
Inventor 李学涛孔亮臧娟刘扬郭睿博张璐
Owner LIAONING UNIV OF TRADITIONAL CHINESE MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap