Sodium fluorescein contrast agent modified by polyethyleneimine and its preparation method and application

A technology of polyethylenimine and fluorescein sodium, which is applied in preparations for in vivo experiments and pharmaceutical formulations, can solve problems such as patients’ inability to get a diagnosis early, delay in treatment timing, and adverse reactions of patients, so as to reduce tissue adsorption, The effect of maintaining the contrast effect and reducing the toxic effect

Active Publication Date: 2022-01-11
SHANGHAI TENTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although fluorescein sodium contrast agent has been widely used clinically, there are still certain limitations, for example: (1) Some patients still have adverse reactions, such as nausea, vomiting, rash, and even lead to anaphylactic shock and death
This prevents patients from being diagnosed early and delays the timing of treatment
(2) Sodium fluorescein molecules can leak from the choroidal capillaries to the outside of the blood vessels, so sodium fluorescein angiography is mainly used for retinal angiography, such as diabetic retinopathy, retinal vein or artery blockage, leakage, etc. Choroidal angiography is less effective
In the prior art, there is no report about the sodium fluorescein contrast agent modified by polyethyleneimine of the present invention

Method used

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  • Sodium fluorescein contrast agent modified by polyethyleneimine and its preparation method and application
  • Sodium fluorescein contrast agent modified by polyethyleneimine and its preparation method and application
  • Sodium fluorescein contrast agent modified by polyethyleneimine and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Preparation and Characterization of PEI-NHAc-FS

[0036] 1 Preparation of PEI-NHAc-FS

[0037] Sodium fluorescein (200 mg, 1 ml) was stirred with 10 molar equivalents of EDC·HCl for 30 minutes and then with 10 molar equivalents of NHS for an additional 3 hours to form an orange solution. Then, PEI (380 mg, 5 mL) with a molecular weight of 25,000 was added to the above solution and stirred vigorously for 3 days to obtain PEI-NH 2- FS. Afterwards, the PEI-NH 2- FS acetylation. Briefly, acetic anhydride (1 mL), which exceeded five times the molar equivalent of the remaining amino groups on PEI, was added to the above mixture and stirred for 24 hours, after which the mixture was thoroughly dialyzed for 3 days and freeze-dried to obtain PEI-NHAc-FS.

[0038] 2 Characterization of PEI-NHAc-FS

[0039] In order to observe the characteristics of the synthesized nanomaterials, FS, PEI, PEI-NH 2 -FS and PEI-NHAc-FS for characterization analysis, mainly including: ...

Embodiment 2

[0046] Example 2 Safety and effectiveness of PEI-NHAc-FS at the cellular level

[0047] 1 Experimental method

[0048] 1.1 CCK8 experiment

[0049] Take the ARPE-19 and HUVEC cells in the logarithmic growth phase, and take 10 4 Place cells / well into 96-well plates, put them in an incubator and cultivate them for 24 hours, and wait for the cells to adhere to the wall. Add 1-10μmol / L FS and PEI-NHAc-FS respectively, and incubate for 24h. Change the medium, add 110 μL of medium containing 10 μL of CCK-8 to each well, and incubate at 37°C for 2 hours in the dark. For detection on the machine, a wavelength of 450nm is selected, and the OD value of each well is detected on a multifunctional microplate reader.

[0050] 1.2 Detection of apoptosis by flow cytometry

[0051] Take the ARPE-19 and HUVEC cells in the logarithmic growth phase, and use 5×10 4 Each cell / well was spread into a 12-well plate, and cultured in an incubator for 24 hours until the cells adhered to the wall. ...

Embodiment 3

[0063] Example 3 Safety and effectiveness of PEI-NHAc-FS at animal level

[0064] 1 Experimental method

[0065] 1.1 Establishment of laser-induced CNV model in rats with BN

[0066] BN male rats (8-10 weeks, mass 180±20g), anesthetized by intraperitoneal injection of 1% pentobarbital sodium 40mg / mg, mydriasis with compound tropicamide, surface anesthetized with alcaine, exposed right eye , holding a cover glass as a contact lens, laser photocoagulation between 2 retinal vessels from the optic disc, a total of 6-8 points, using laser (532nm, 360mW, 0.1s, 50μm) to establish a rat CNV model, after photocoagulation Bubbles or mild bleeding shall prevail. Pay attention to avoid fundus blood vessels during laser treatment to avoid severe fundus hemorrhage.

[0067] 1.2 Preparation of paraffin sections

[0068]The above 6 BN rats were divided into 2 groups, control group (injection of normal saline into tail vein, n=3), PEI-NHAc-FS group (injection of 1% PEI-NHAc-FS 0.15mL in ta...

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Abstract

The invention discloses a polyethyleneimine-modified sodium fluorescein contrast agent for fundus angiography, and the contrast agent refers to dendrimer polyethyleneimine-modified sodium fluorescein PEI-NHAc-FS. The invention also discloses the preparation method of the above-mentioned contrast agent and its application in the preparation of fundus blood vessel contrast agent. The invention successfully constructs polyethylenimine-modified fluorescein sodium, verifies the safety and effectiveness of PEI-NHAc-FS at the cell and animal levels, and provides a safety guarantee for the use of the nanomaterial in fundus angiography. Compared with the existing contrast agents, PEI‑NHAc‑FS has the advantages of low endocytosis rate, weaker adhesion between tissues, clear retinal imaging, and faster fundus blood vessel metabolism. The present invention accelerates intraocular metabolism while completing retinal fundus angiography, reduces the toxicity, sensitization and retention time of traditional contrast agents, and reduces side effects.

Description

technical field [0001] The invention relates to the technical field of fundus angiography, in particular to polyethyleneimine-modified sodium fluorescein contrast agent and its preparation method and application. Background technique [0002] Age-related macular degeneration (age-related macular degeneration, AMD) is one of the most important causes of central vision loss and irreversible blindness in the elderly over 50 years old. Currently, there are about 21 million AMD patients in the world. AMD is divided into dry and wet types according to the presence or absence of neovascularization. Early dry AMD manifests as drusen, which does not have a serious impact on vision. In the late stage, geographic atrophy, discoid degeneration, etc. will occur, resulting in vision loss. In wet AMD, due to the appearance of choroidal neovascularization (CNV) in the macular area, macular hemorrhage, edema, and severe vision loss are caused. Currently, the diagnostic methods for AMD incl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00
CPCA61K49/0043A61K49/0054
Inventor 于靖彭琛蔡雯婷金惠子余咚卉范佳琪
Owner SHANGHAI TENTH PEOPLES HOSPITAL
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