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Application of linoleic acid coupled prodrug of mycophenolate mofetil in anti-fibrosis or/and anti-tumor drugs

A technology of mycophenolate mofetil and anti-tumor drugs, which is applied in the direction of anti-tumor drugs, drug combinations, medical preparations of non-active ingredients, etc., and can solve the problem of low tumor target lethality, limited therapeutic effect, and short retention time To achieve the effect of prolonging the circulation time in the body, increasing drug accumulation and reducing toxicity

Pending Publication Date: 2022-06-03
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the single MMF nano-preparation has poor water solubility, short retention time in the body, and low targeted lethality to tumors, so the therapeutic effect is limited.

Method used

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  • Application of linoleic acid coupled prodrug of mycophenolate mofetil in anti-fibrosis or/and anti-tumor drugs
  • Application of linoleic acid coupled prodrug of mycophenolate mofetil in anti-fibrosis or/and anti-tumor drugs
  • Application of linoleic acid coupled prodrug of mycophenolate mofetil in anti-fibrosis or/and anti-tumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Synthesis of MMF-LA conjugated prodrugs, such as figure 1 shown:

[0054] MMF (65 mg, 0.15 mmol), linoleic acid (42.1 mg, 0.15 mmol) and DMAP (18.3 mg, 0.15 mmol) were sequentially added to a 100 mL round-bottomed flask, dissolved in 4 mL of anhydrous dichloromethane, and then EDC was added dropwise rapidly (23.3 mg, 0.15 mmol). The mixture was stirred at 43°C for 3 hours, and the reaction state was observed by thin layer chromatography. When the reaction was basically completed, the reaction solution was cooled, washed with 0.1M hydrochloric acid solution, saturated sodium bicarbonate, and saturated brine respectively; the organic phase was dried with anhydrous sodium sulfate, filtered, and the filtrate was collected and the solvent was removed under reduced pressure; through column chromatography After chromatographic separation and purification (DCM:MeOH=20:1), the product MMF-LA conjugated prodrug (47 mg, yield 45.1%) was obtained.

[0055] The product MMF-LA con...

Embodiment 2

[0058] (1) Preparation of PEGylated MMF-LA nanoformulations:

[0059] The PEGylated MMF-LA conjugated prodrug prepared in Example 1 was dissolved in DSPE-PEG containing 2k In the dimethyl sulfoxide solvent, a mixed solution was obtained, in which the PEGylated MMF-LA conjugated prodrug and DSPE-PEG 2k The mass ratio of MMF-LA is 10:1; and the mixed solution is injected into the aqueous phase under ultrasonic conditions (the volume ratio of dimethyl sulfoxide and the aqueous phase is 1:9), and the uniformly dispersed PEGylated MMF-LA nanoparticles are obtained by dialysis. formulation, denoted DSPE-PEG 2k Coated MMF-LA nanoformulations.

[0060] as DSPE-PEG 2k The control group coated with MMF-LA nanoformulations, polyacetic acid-polyethylene glycol (PEG 5K -PLA 8K ) in place of the above DSPE-PEG 2k , using the above method to prepare polyacetic acid-PEGylated MMF-LA nano-formulations, denoted as PEG 5K -PLA 8K Coated MMF-LA nanoformulations.

[0061] (2) In vitro kil...

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Abstract

The invention provides an application of a linoleic acid coupled prodrug of mycophenolate mofetil in anti-fibrosis or / and anti-tumor drugs. The linoleic acid coupled prodrug of mycophenolate mofetil is applied to an anti-fibrosis drug or / and an anti-tumor drug, direct release of the drug in blood can be reduced, and a higher fibroblast targeting effect is achieved, so that a better anti-fibrosis effect is achieved; and a stronger anti-tumor effect is realized by reducing the fibrosis level in the tumor and increasing the drug accumulation in the tumor.

Description

technical field [0001] The invention belongs to the technical field of anti-fibrosis and anti-tumor drugs, in particular to the application of a linoleic acid conjugated prodrug of mycophenolate mofetil in anti-fibrosis drugs or / and anti-tumor. Background technique [0002] Mycophenolate mofetil (MMF) active ingredient MPA (mycophenlic acid, MPA) is a non-competitive and reversible inosine monophosphate dehydrogenase inhibitor, because it can effectively inhibit T, B Lymphocyte proliferation is widely used to prevent and treat acute rejection after organ transplantation. With the deepening of research, it is found that MMF has a significant inhibitory effect on fibroblasts and tumor cells, so it may be used in anti-fibrosis and anti-tumor therapy. However, the water solubility of MMF is extremely poor, and it is mainly used for oral administration in clinical practice. [0003] Nanoformulation technology is considered to be an effective means to improve the in vivo bioavai...

Claims

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Application Information

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IPC IPC(8): A61K47/54A61K31/5377A61K9/51A61K47/24A61P43/00A61P35/00
CPCA61K47/542A61K31/5377A61K9/5146A61P43/00A61P35/00
Inventor 谢海洋杨振涛王杭祥朱海万建钦
Owner ZHEJIANG UNIV