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Manganese-containing micro-precipitation liposome for immunotherapy and preparation method thereof

A technology of liposomes and phospholipids, which is applied in the direction of liposome delivery, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., which can solve the problems of toxic side effects of the immune system, damage to the central nervous system, and easy distribution , to achieve good biocompatibility, reduce central nervous system toxicity, and reduce central nervous system toxicity

Active Publication Date: 2020-09-11
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the use of divalent manganese ions in immunotherapy still has the following problems: it cannot achieve specific distribution after administration in the body, and it is easily distributed to the nervous system, damaging the central nervous system, and will also cause certain toxic side effects on the immune system
In addition, exogenous manganese ions enter cells mainly through concentration gradient diffusion, and cannot specifically enter target cells but not non-target cells.

Method used

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  • Manganese-containing micro-precipitation liposome for immunotherapy and preparation method thereof
  • Manganese-containing micro-precipitation liposome for immunotherapy and preparation method thereof
  • Manganese-containing micro-precipitation liposome for immunotherapy and preparation method thereof

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Effect test

Embodiment 1

[0069] Embodiment 1, the preparation that contains manganese hydrogen phosphate liposome

[0070] Manganese chloride was formulated into a 500 mM aqueous solution, and 300 μL of this solution was added dropwise to 15 mL of cyclohexane / nonoxynol mixed oil solution (70 / 30, v / v) under ultrasonication, and the ultrasonication was continued. The water droplets are cracked and evenly dispersed in the oil phase;

[0071] Sodium hydrogen phosphate was prepared into a 25 mM aqueous solution, and 300 μL of this solution was added dropwise to 15 mL of cyclohexane / nonoxynol mixed oil solution (70 / 30, v / v) under ultrasonication, and the ultrasonication was continued. The water droplets were cracked and evenly dispersed in the oil phase, and then 200 μl of 20 mg / mL DOPA chloroform solution was added;

[0072] Mix the above two solutions and let stand for 30 minutes to make manganese ions react with hydrogen phosphate ions to form a micro-precipitate, then add ethanol with a volume equivale...

Embodiment 2

[0075] Embodiment 2, the preparation that contains manganese phosphate liposome

[0076] Manganese chloride was prepared into a 1M aqueous solution, and 600 μL of the solution was added dropwise to 30 mL of cyclohexane / nonoxynol mixed oil solution (70 / 30, v / v) under ultrasonication, and the ultrasonication was continued. The water droplets are cracked and evenly dispersed in the oil phase;

[0077] Sodium phosphate was prepared into a 50 mM aqueous solution, and 600 μL of this solution was added dropwise to 30 mL of cyclohexane / nonoxynol mixed oil solution (70 / 30, v / v) under ultrasonication, and the ultrasonication was continued to make The water droplets were cracked and evenly dispersed in the oil phase, and then 200 μL of 20 mg / mL DOPA in chloroform was added;

[0078] Mix the above two solutions and let them stand for 30 minutes to make manganese ions react with phosphate ions to form micro-precipitates, then add ethanol equivalent in volume to the oil phase solution to d...

Embodiment 3

[0080] Embodiment 3, the preparation that contains manganese carbonate liposome

[0081] Manganese chloride was formulated into a 500 mM aqueous solution, and 300 μL of this solution was added dropwise to 15 mL of cyclohexane / nonoxynol mixed oil solution (70 / 30, v / v) under ultrasonication, and the ultrasonication was continued. The water droplets are cracked and evenly dispersed in the oil phase;

[0082] Sodium carbonate was prepared into a 25 mM aqueous solution, and 300 μL of this solution was added dropwise to 15 mL of cyclohexane / nonoxynol mixed oil solution (70 / 30, v / v) under ultrasonication, and the ultrasonication was continued to make The water droplets were cracked and evenly dispersed in the oil phase, and then 200 μL of 20 mg / mL DOPA in chloroform was added;

[0083] Mix the above two solutions and let stand for 30 minutes to make manganese ions react with carbonate ions to form micro-precipitates, then add ethanol equivalent in volume to the oil phase solution to...

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Abstract

The invention discloses a manganese-containing micro-precipitation liposome for immunotherapy and a preparation method thereof. The liposome consists of a micro-precipitation inner core containing manganese ions and a phospholipid bilayer shell, and can be prepared by combining an emulsion mixing method and a film dispersion method. The liposome has a spherical structure of 20-200nm, has a certainamount of positive charges on the surface, and can be degraded in a certain acid environment. The liposome can stimulate an inherent immune system and / or adaptive immunity or serve as an immunologicadjuvant, and is used for treating related diseases such as virus resistance, bacteria resistance, tumor resistance, autoimmune diseases and the like.

Description

technical field [0001] The invention relates to a manganese-containing microprecipitated liposome (NanoMn) for immunotherapy or cancer treatment and a preparation method thereof, belonging to the field of nano preparations. Background technique [0002] As one of the essential trace elements for the human body, manganese metal plays a variety of extremely important physiological functions in the body. In recent years, it has been reported that divalent manganese ions play an important immune function in the body, and are natural immune activators and alarms in cells. Innate immunity is the first line of defense for host cells against the invasion of pathogenic microorganisms. A number of studies have shown that the cGAS-STING signaling pathway is an important pathway for immune activation in the body. It can sense virus invasion in antiviral immunity, activate transcription factors IRF3 / 7 and NF-κB, and produce type I interferon ( IFN) and other antiviral cytokines; it als...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K33/32A61K39/39A61K47/54A61K47/64A61P31/04A61P31/12A61P35/00A61P37/04
CPCA61K9/0019A61K9/1277A61K33/32A61K39/39A61K2039/55505A61K47/545A61K47/64A61K47/644A61P31/04A61P31/12A61P35/00A61P37/04Y02A50/30
Inventor 林志强游富平吕丹梁子超雒钰杰王晓
Owner PEKING UNIV
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