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Use of diketone compounds in photodynamic therapy or diagnosis

A compound and application technology, applied in the field of medicine, can solve problems such as limited application and reduced photochemical efficiency, and achieve good safety, good bioavailability, and immune-enhancing effects

Active Publication Date: 2022-06-21
BEIJING WHOLESOMETECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the existence of the large π-conjugated ring system of this type of photosensitizer, there is a strong π-π stacking interaction between the molecules, which leads to the aggregation of porphyrin and / or phthalocyanine molecules and reduces its photochemical efficiency. greatly limit its clinical application

Method used

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  • Use of diketone compounds in photodynamic therapy or diagnosis
  • Use of diketone compounds in photodynamic therapy or diagnosis
  • Use of diketone compounds in photodynamic therapy or diagnosis

Examples

Experimental program
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Effect test

experiment example 1

[0126] Experimental Example 1. Evaluation of Compound Toxicity to Tumor Cytotoxicity

[0127] In this experimental example, the toxicity of compounds to tumor cells was detected by MTT method, and the specific steps were as follows:

[0128] (1) Collect log-phase cells, adjust the concentration of cell suspension, add 100 μL to each well, and plate the cells to adjust the density to 1000-10000 wells (the edge wells are filled with sterile PBS).

[0129] (2)5%CO 2 , incubate at 37°C until the cell monolayer covers the bottom of the well (96-well flat bottom plate), and add the drug in a concentration gradient. Generally 5-7 gradients, 100 μL per well, set 3-5 duplicate wells.

[0130] (3) The cells were randomly divided into light-administration and light-protection-administration groups, 5% CO 2 , incubated at 37°C for 16-48 hours, and observed under an inverted microscope.

[0131] (4) Laser light with wavelength of 450nm-480nm (light intensity 15mW / cm 2 ) irradiated the...

experiment example 2

[0144] Experimental Example 2. Evaluation of Inhibitory Effects of Compounds on Bacteria

[0145] A single E. coli colony was transferred from a solid Luria Bertani (LB) agar plate to 5 ml of liquid LB medium and incubated at 37°C for 12 hours. Bacteria were collected by centrifugation (7000 rpm, 1 min) and three washes with PBS buffer. Discard the supernatant and resuspend the remaining E. coli in PBS buffer. Adjust the optical density (OD600) of the bacterial suspension to 1.0. The suspension was then diluted (5-fold) with PBS buffer. The diluted E. coli cell suspension was incubated with a 60mM photosensitizer (diketone) solution at 37°C in the dark for 15 minutes, and then at 15mW / cm 2 Illumination under laser light for 200s (wavelength 450nm-480nm, final illumination intensity 3J cm -2 ), serial dilutions of the illuminated bacterial suspension (10 4 times). 100 [mu]L of the diluted bacterial E. coli was spread on solid LB agar plates, incubated at 37[deg.]C for 12-...

experiment example 3

[0149] Experimental Example 3. Evaluation of the Inhibitory Effect of Compounds on Tumors (Animal Experiment)

[0150] 1. Using BJMU-204 as a photosensitizer, BALB / C mice were used for photodynamic therapy of tumor.

[0151] Modeling method: BALB / C mice were divided into 5 groups with 11-12 mice in each group. Resuscitate and subculture 4T1 (mouse breast cancer cells) to a better cell state for tumor inoculation. BALB / C mice were subjected to local depilation and disinfection, and tumor cells were injected into the mouse mammary fat pad in situ. 7-10 days for tumor formation.

[0152] Administration time: drug intervention was given after the mice formed tumors, and photodynamic therapy was performed by intratumoral injection every other day (wavelength 450nm-480nm laser, light intensity 200mW / cm) 2 ).

[0153] Mode of administration: see the table below, the photosensitizer was dissolved in physiological saline, and the mice in groups 1-3 were injected intratumorally, and...

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Abstract

The invention belongs to the technical field of medicine and relates to the application of diketone compounds in photodynamic therapy or diagnosis. In particular, the present invention relates to compounds represented by formula (I), their pharmaceutically acceptable salts or esters, prodrugs, stereoisomers, hydrates, solvates, crystal forms, their metabolite forms, or Use of any combination or mixture thereof in the preparation of medicines or reagents for photodynamic therapy or photodynamic diagnosis of diseases.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the use of diketone compounds in photodynamic therapy or diagnosis. Background technique [0002] Photodynamic therapy (Photodynamic Therapy) is a kind of photochemotherapy, which is based on photosensitizer sensitization to induce oxygen to generate reactive oxygen species (ROS) represented by singlet oxygen, which can kill tumor cells or pathogenic microorganisms in order to achieve treatment. the purpose of the disease. Photodynamic therapy is a new type of therapy, which has been used in some clinical treatments including: tumors, condyloma acuminatum, acne and port-wine stains. Among them, compared with the traditional therapy of tumor treatment, photodynamic therapy has the obvious advantages of convenient operation, high selectivity and less side effects. [0003] Photodynamic diagnosis refers to the diagnosis of diseases using the characteristic spectrum of photosensitiz...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61P35/00A61P33/00A61P31/00A61P37/02G01N33/574C07C49/12C07C49/16C07C59/84C07C59/19C07C49/784C07D213/50C07D307/46C07C49/84C07C49/813
CPCA61K41/0057A61P35/00A61P37/02A61P35/02A61P31/04A61P33/02A61P33/14A61P33/10A61P31/10A61P31/14A61P31/20A61P31/18A61K49/0021A61P33/00A61P31/00C07D213/50C07D307/46A61K31/12Y02A50/30A61K31/121A61K31/444A61K31/341A61K8/35A61K8/365A61K8/4926A61K8/69A61K8/4973A61Q19/08A61Q19/00A61Q17/005A61K2800/81C07D401/06C07D407/06C07C49/12C07C59/84C07C59/19C07C49/784C07C49/813G01N33/574
Inventor 焦宁魏佳良刘雅萌
Owner BEIJING WHOLESOMETECH CO LTD
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