Synthesis and application of photosensitive medicament taking folic acid as targeted group

A photosensitive and targeted technology, which can be used in drug combinations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc. It can solve problems such as hindering application, limited ability of Pyro tumor localization, and tissue damage.

Active Publication Date: 2017-01-04
康宏药源(河南)科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Pyro's limited tumor localization ability and poor water solubility make it cause damage to no

Method used

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  • Synthesis and application of photosensitive medicament taking folic acid as targeted group
  • Synthesis and application of photosensitive medicament taking folic acid as targeted group
  • Synthesis and application of photosensitive medicament taking folic acid as targeted group

Examples

Experimental program
Comparison scheme
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Example Embodiment

[0034] Example 1

[0035] Synthesis of the compound referred to as Pyro-Maleimide and the compound referred to as FA-Pyro (attached figure 1 ).

[0036] The synthesis process integrates a solid phase synthesis method and a liquid phase synthesis method, simplifies the post-processing process, and facilitates mass preparation. Among them, the synthesis of FA-Pyro adopts the classic way of sulfhydryl and maleimide reaction, which greatly improves the yield of the compound.

[0037] 1. Synthesis of compounds referred to as FA-Cys-SH

[0038] FA-Cys-SH is synthesized using Fmoc-based solid-phase synthesis. Weigh 1 g of 2-chlorotritylchloride resin (1 g, 0.5 mmol, 1.0 eq) in a solid phase synthesizer, and add 10 ml of dichloromethane (DCM) to swell for 20 minutes. Dissolve Fmoc-Cys(Trt)-OH (351mg, 0.6mmol, 1.2eq) and N,N-diisopropylethylamine (DIEA, 198μl, 1.2mmol, 2.4eq) with 8ml DCM and add to the solid phase synthesis In the vessel, react at room temperature for 4h. A sealing liquid...

Example Embodiment

[0046] Example 2

[0047] The spectral properties of FA-Pyro and Pyro (attached figure 2 ).

[0048] (1) UV-Vis spectrum

[0049] The absorption spectra of FA-Pyro and Pyro were scanned in the wavelength range of 300-850 with USA Cary 5000. The concentrations of FA-Pyro and Pyro are 10 μM, respectively.

[0050] (2) Fluorescence excitation and emission spectra

[0051] The fluorescence emission spectrum uses 665nm as the excitation light, and the recorded spectrum range is 600-900nm. The fluorescence excitation spectrum uses 675 as the emission light, and the recording excitation light range is 450-800nm. The concentration of FA-Pyro and Pyro was recorded as 5 μM. The photomultiplier tube (PMT) voltage is 700V, and the scanning speed is 2400nm / min.

[0052] Experimental results and conclusions:

[0053] The spectral properties of FA-Pyro and Pyro, namely absorption and fluorescence spectra, are figure 2 Shown in A and 2B: In DMSO, the spectral properties of FA-Pyro are similar to th...

Example Embodiment

[0054] Example 3

[0055] Compound FA-Pyro kills tumor cells (attached image 3 ).

[0056] 1) Culture of KB (human oral epidermal carcinoma cell) and A549 (human lung bronchial carcinoma cell) cell lines

[0057] Remove the cells in liquid nitrogen, place them in a 37°C water bath and thaw them quickly, then centrifuge at 1000 rpm / min for 5 minutes. Discard the supernatant, add pre-warmed complete medium, and place it in a 5% CO2, 37°C incubator overnight. Change the medium the next day. Continue to culture until the cells cover the bottom of the dish. Subculture 2-3 times.

[0058] 2) Incubation of drugs and cells

[0059] Take the cells in the logarithmic phase to 5×10 3 Add 100μL of cell suspension to a 96-well plate with a cell density of one cell / well, and incubate for 24h in a 37°C incubator. After aspirating the medium, add fresh medium containing different FA-Pyro concentrations and continue culturing for 6 hours, then use 660nm, 40-mW / cm 2 Give different light doses (0min...

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Abstract

The invention discloses synthesis and application of a photosensitive medicament taking folic acid as a targeted group. Micro-molecular folic acid is selected to serve as the targeted group to link Pyro. Because of the water solubility of the folic acid and a hydrophilic group in a linker, the linker can improve the water solubility and the pharmacokinetic characteristics of the Pyro so as to improve a photodynamic treatment effect.

Description

technical field [0001] The present invention relates to the synthesis of photosensitive drug called FA-Pyro for short and its application in tumor photodynamic therapy. Background technique [0002] At present, the clinical methods for treating cancer mainly include radiotherapy, chemotherapy and surgery. However, while these traditional treatment methods kill tumor tissues, they also damage normal tissues of the body and cause systemic toxicity. Photodynamic therapy (Photodynamic Therapy, PDT), as a minimally invasive treatment strategy for clinical application, has attracted more and more attention. [0003] The therapeutic effect of PDT needs to be combined with the following three elements: 1. A photosensitizer that can be enriched in tumor tissue; 2. Light of a specific wavelength required to excite the photosensitizer; 3. Oxygen (O 2 ). When the photosensitizer is excited by light of a specific wavelength, it utilizes the O in the tissue 2 Singlet oxygen is generat...

Claims

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Application Information

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IPC IPC(8): C07D519/00A61K41/00A61K47/48A61P35/00
CPCA61K41/0071C07D519/00
Inventor 洪章勇黄伟强
Owner 康宏药源(河南)科技有限公司
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