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Application of CaPB nanoparticles in preparation of drugs for treating retinal degenerative diseases

A technology for retinal degeneration and disease treatment, which can be used in drug combination, sensory disease, drug delivery, etc., can solve the problems of mitochondrial iron homeostasis destruction and limited effect, and achieve the effects of good biocompatibility, long-term efficacy and simple preparation.

Pending Publication Date: 2022-01-04
SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, iron overload in RPE also involves disruption of mitochondrial iron homeostasis, suggesting a limited role for DFO in alleviating iron overload and oxidative stress-induced RPE damage

Method used

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  • Application of CaPB nanoparticles in preparation of drugs for treating retinal degenerative diseases
  • Application of CaPB nanoparticles in preparation of drugs for treating retinal degenerative diseases
  • Application of CaPB nanoparticles in preparation of drugs for treating retinal degenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Preparation Example 1 CaPB embodiment nanoparticles

[0042] The 88.8mg of calcium chloride was dissolved in 10mL pH = 1 of deionized water to prepare a solution;

[0043] The 263.4mg potassium ferricyanide was dissolved in deionized water and 40mL pH = 1, 2 to obtain a solution;

[0044] The 300mg PVP (1w) was dissolved in deionized water and 30mL pH = 1, and 3 to obtain a solution;

[0045] The mixed solution 1 and 3, at a rate of 1 second is added dropwise a solution of 2, 1 hour of reaction, i.e. prepared CaPB nanoparticles having an average spherical particles (including PVP) diameter of about 36nm, such as image 3 Indicated.

[0046] The present invention is mediated by a simple polymer nucleation, calcium ions are uniformly doped Prussian Blue analogs constructed surface having a biocompatible polyvinyl pyrrolidone to form a modified nanoparticles.

Embodiment 2

[0047] Example 2 CaPB nanoparticles reduced ferrous ion levels in RPE in vitro

[0048] This embodiment employs vitro experiments, i.e. retinal pigment epithelial cell line (ARPE-19) as the research object, verified experimentally CaPB nanoparticles oxidative stress-inducing agent is sodium iodine (NaIO4 3 ) Protective effect induced retinal degeneration (typically cell model retinal degenerative diseases of dry AMD) is, we use the ferrous chelates desferrioxamine (the DFO) as a positive control.

[0049] By FerroOrange probe staining, we found NaIO 3 ARPE-19 cells (3OmM) in culture, significantly increased levels of ferrous ions, and CaPB (40ppm) and DFO (75μM) significantly decreased after treatment of NaIO 3 Levels induced by ferrous ions ( Figure 4 ), Suggesting CaPB significant iron binding capacity.

Embodiment 3

[0050] Example 3 CaPB nanoparticles protective retinal pigment epithelial cell degeneration

[0051] We further investigated whether nanoparticles CaPB similar therapeutic effects in vitro and in vivo. NaIO 3 The method of treatment of mice by tail vein injection of 35mg / kg of NaIO 3 A method for in vivo administration by intravitreal injection the mice at a concentration of 200ppm of 1μL CAPB, 1μL or DFO 100μM concentration; the time of administration is intravitreal injection CAPB DFO 15 minutes before or by NaIO 3 Tail vein injection. Sample detection was isolated from the mouse retina through the respective treatment RPE primary cells, abbreviated mRPE.

[0052] By mRPE elemental analysis, we found NaIO 3 Ferrous ion levels of treated group gradually increased over time ( Figure 5 Left), when treated with NaIO nanoparticles CaPB 3 Mouse retinas injected 2 weeks, 3 weeks and 4 weeks later, mRPE ferrous ion levels continued to decrease over time ( Figure 5 Right), indicating C...

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Abstract

The invention discloses an application of calcium-substituted prussian blue analogue (CaPB) nanoparticles in preparation of a medicine for treating a retinal degenerative disease. The inner core of the nano-particle is of a calcium ion uniformly doped Prussian blue skeleton structure, the surface of the nano-particle is modified with polyvinylpyrrolidone with biocompatibility, and the nano-particle can be formed by self-assembling ferricyanide ions, calcium ions and polyvinylpyrrolidone. The nanoparticles can enter cells and can be selectively combined with iron in the cells through a simple ion exchange method, so that diseases related to retinal pigment epithelial cell degeneration caused by ferrous ions serving as oxidative stress sources are prevented; and the application is a promising alternative scheme for treating oxidative stress mediated retinal cell injury diseases.

Description

Technical field [0001] The present invention relates to the treatment of retinal degenerative diseases, and more particularly to a calcium-substituted iron-binding prumbers blue analog nanoparticles in the preparation of retinal degenerative disease treatment drugs. Background technique [0002] The retinal pigment epithelial cell (RPE) is supported in the retinal oxygen-enriched environment, which is supported by the normal function and survival of photoreceptor cells, which mainly uses various biological effects, including epithelial transport liquids and nutrients, and constitutes an external blood-retinal film. Barrier, phased debris, etc. Therefore, RPE dysfunction can lead to a variety of eye diseases, and with different degrees of vision damage or even blindness, which is one of the most incident of age-related macular degeneration (AMD). At present, the prevalence of AMD in 45 years old and over the world is about 8.7%. AMD is divided into two major types of non-new vesse...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K47/32A61K33/26A61P27/02A61P9/10
CPCA61K9/1635A61K33/26A61K9/0048A61P27/02A61P9/10
Inventor 谷平汤志敏陈雨霍敏锋
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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