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Targeting phase-change nano-drug system as well as preparation method and application thereof

A nano-drug, targeting technology, applied in the field of biomedicine, can solve problems such as toxicity and side effect targeting, achieve good stability, reduce the level of reactive oxygen species in podocytes, and improve the effect of catalase activity

Active Publication Date: 2020-08-21
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a targeted phase-change nano drug system to solve the problems of toxic side effects and weak targeting in the prior art when immune-related kidney diseases are treated with immunosuppression

Method used

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  • Targeting phase-change nano-drug system as well as preparation method and application thereof
  • Targeting phase-change nano-drug system as well as preparation method and application thereof
  • Targeting phase-change nano-drug system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Example 1: Preparation of targeted phase-change nano-medicine system (DEX / PFP@LIPs-BMS-α)

[0065] (1) Synthesis of DSPE-PEG-COOH—BMS-α

[0066] Using distearoylphosphatidylethanolamine-polyethylene glycol-carboxyl (DSPE-PEG(2000)-COOH) and compound BMS-470539 (abbreviated as BMS-α) as raw materials, the condensed Compounds (distearoylphosphatidylethanolamine-polyethylene glycol-carboxy-BMS-α, DSPE-PEG-COOH-BMS-α).

[0067] Take 80mg (0.027mmol) of DSPE-PEG(2000)-COOH, dissolve it in 20ml of dimethylformamide (DMF); add 3.8mg (0.027mmol) of anhydrous 1-hydroxybenzotriazole (HOBT); Add 3.5mg (0.027mmol) N, N-diisopropylcarbodiimide (DIC), shake for 0.5h; then add 15mg (0.025mmol) compound BMS-470539 dissolved in 2ml DMF, shake at room temperature for 24h; The target product DSPE-PEG-COOH—BMS-α was obtained through purification. The final target product was detected by Mass Spectrometry and HPLC, and the target product was determined to be DSPE-PEG-COOH—BMS-α.

[0068...

Embodiment 2

[0075] Example 2: Preparation of targeted phase-change nano-medicine system (PFP@LIPs-BMS-α)

[0076] The preparation method of the present embodiment is the same as embodiment 1, and the difference is in step (2), specifically as follows:

[0077] (2) Preparation of lipid film

[0078] Dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), the compound (DSPE-PEG-COOH-BMS-α) prepared in step (1) and cholesterol (CHO) were prepared according to the ratio of 69:8 : The molar ratio of 8:15 was placed in a round bottom flask, and Dil was added at the same time. The dosage of Dil is 0.5 mg Dil per 10 mg lipid (lipid includes DPPC, DPPG, DSPE-PEG-COOH-BMS-α and CHO four substances). Then add 5ml of chloroform and 2ml of methanol to fully dissolve. The lipid film was obtained by rotary evaporation for 30 min in an environment with a water bath temperature of 55° C. and a negative pressure of -0.1 MPa.

Embodiment 3

[0079] Embodiment 3: Preparation of phase change nano drug system (PFP@LIPs)

[0080]The present embodiment is basically the same as Example 2, the difference is: do not use DSPE-PEG-COOH-BMS-α (that is, no (1) DSPE-PEG-COOH-BMS-α synthesis), in (2) and (3 ) in the synthesis step, use DSPE-PEG-COOH instead of DSPE-PEG-COOH—BMS-α. Potential analysis was carried out on the PFP@LIPs prepared by this scheme, and the results were as follows image 3 As shown, the average Zeta potential was (-42.3±0.9)mV.

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Abstract

The invention relates to the technical field of biological medicines, in particular to a targeting phase-change nano-drug system as well as a preparation method and application thereof. The targetingphase-change nano-drug system comprises a main body, liquid fluorocarbon is wrapped in the main body, the main body is loaded with a drug, and the main body is covalently connected with BMS-470539. The medicine system can solve the problems of toxic and side effects and weak targeting when immunosuppressive treatment is adopted for immune-related kidney diseases in the prior art. The targeting phase-change nano-drug system can be applied to preparation of related drugs for treating immune nephropathy.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a targeted phase-change nano drug system and its preparation method and application. Background technique [0002] Immune nephropathy is a group of chronic glomerular diseases caused by multiple etiologies with the same immunopathological features. Immune nephropathy includes purpura nephritis, lupus nephritis, IgA nephropathy, etc. Due to the dysfunction of the patient's immune system, the immune complexes produced are deposited in the kidney, causing damage to the intrinsic cells of the kidney, causing inflammatory reactions, etc., destroying the intrinsic The normal function of the cells causes the patient to have symptoms of kidney disease such as proteinuria, hematuria, and edema. [0003] Immune-related kidney disease, such as membranous nephropathy (MN), is one of the common pathological types of nephrotic syndrome. The global annual incidence of MN is 1.2 / 100,000, mo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K47/54A61K47/06A61K31/573A61P13/12A61P37/06
CPCA61K9/5015A61K31/573A61K47/06A61P13/12A61P37/06
Inventor 曾粒凡奎钟玲王志刚冉海涛郝兰
Owner CHONGQING MEDICAL UNIVERSITY
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