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Nano-MOF (metal organic framework) photosensitizer based on bacteriochiorin and preparation method

A nano-metal and organic framework technology, applied in the field of photosensitizers, can solve the problems of long, dark time for more than 4 weeks to be excreted from the body, short photosensitive period, etc., to improve drug accumulation, simple structure, and prevent aggregation and quenching. Effect

Active Publication Date: 2019-04-26
UNIV OF SCI & TECH BEIJING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The first-generation photosensitizers include hematoporphyrin derivatives, dihematoporphyrin ether and Photofrin, etc., which have been approved by the drug regulatory departments of many countries for clinical use, but the retention time in the body is too long, and the light-proof time needs to be more than 4 weeks In addition, the light penetration depth of the first-generation sensitizers is less than 0.5cm, which limits the application of PDT in deep tumors; the second-generation photosensitizers include: m-tetrahydroxyphenyl chlorin, benzene Porphyrin derivatives, phthalocyanines, dexa porphyrin, n-aspartoyl chlorin and other porphyrin derivatives, they partially overcome the shortcomings of the first generation of photosensitizers, more in line with the ideal photosensitizer Features, such as short photosensitive period, light wavelength in the infrared or near-infrared region and strong absorption, tissue penetration depth is greatly improved compared with the first generation of photosensitizers, singlet oxygen production rate and biocompatibility are also significantly improved, Currently in clinical research phase

Method used

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  • Nano-MOF (metal organic framework) photosensitizer based on bacteriochiorin and preparation method
  • Nano-MOF (metal organic framework) photosensitizer based on bacteriochiorin and preparation method
  • Nano-MOF (metal organic framework) photosensitizer based on bacteriochiorin and preparation method

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preparation example Construction

[0040] A preparation method of a nano metal-organic framework photosensitizer based on bacteriochlorin, the steps comprising:

[0041] S1, the metal ion Hf 4+ The corresponding salt is dissolved in N,N-dimethylformamide (DMF) to form Hf 4+ Solution, the p-bacteria chlorophyll is dissolved in DMF, obtains the p-bacteria chlorophyll solution;

[0042] Among them, Hf 4+ The corresponding salts are chlorides or nitrates.

[0043] The structural formula of p-bacteriochlorophyll is

[0044] S2, the configured Hf 4+ The solution is mixed with a p-bacterium chlorophyll solution and an aqueous acetic acid solution, and heated to react to obtain a metal-organic framework material;

[0045] Among them, Hf 4+ The molar ratio of chlorophyll and p-benzoic acid bacteria is 1:1.

[0046] metal ion Hf 4+ and the concentration of the p-bacterium chlorophyll solution is 0.001-0.1mol / L; preferably 0.006mol / L.

[0047] A large amount of acetic acid is used, preferably, the amount of ace...

preparation Embodiment 1

[0052] HfCl 4 Dissolve in DMF to form 2 mg / ml HfCl 4 The solution of p-bacteriochlorin is dissolved in DMF to form a solution of 3.5 mg / ml of p-bacteriochlorin;

[0053] The prepared HfCl 4 The solution and the p-benzoic acid bacteria chlorophyll solution are mixed, and add 0.45ml acetic acid;

[0054] Put the above mixed solution in an oven and react at 90°C for 3 days;

[0055] After cooling to room temperature, centrifuge (6000 rpm) the mixed solution after the reaction, pour out the supernatant, and collect the precipitate;

[0056] The above precipitate was washed with DMF, triethylamine / ethanol (volume ratio of 1:20) and ethanol several times (6000 rpm) until the supernatant had no color, and the precipitate was collected and dried to obtain a solution based on p-benzoic acid Two-dimensional nanometal-organic frameworks of bacteriochlorophyll.

[0057] X-ray diffraction results show that the two-dimensional nano-metal-organic framework crystal based on bacteriochlor...

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Abstract

The invention provides a nano-MOF (metal organic framework) photosensitizer based on bacteriochiorin and a preparation method, and relates to the technical field of photosensitizers. The photosensitizer is easy to prepare and purify, can be used for preparing a drug for treating tumor or subcutaneous layer skin diseases, and has good effect and low toxicity when cooperating with light therapy; crystals of the photosensitizer are of a cubic system, the space groups of the crystals are shown in the description, Mr=5263.82, and the crystallographic parameters are as follows: a=38.758(2) angstrom,b=38.758(2) angstrom, c=38.758(2) angstrom, alpha=90 degrees, beta=90 degrees, gamma=90 degrees, v=58224(5) angstrom<3>, and z=4. The technical scheme is applicable to a process for preparing the drug adopting photodynamic therapy for treating the tumor or the subcutaneous layer skin diseases.

Description

【Technical field】 [0001] The invention relates to the technical field of photosensitizers, in particular to a bacteriochlorin-based nano metal-organic framework photosensitizer and a preparation method. 【Background technique】 [0002] Photodynamic therapy (Photodynamic Therapy, PDT) is a new cancer treatment technology developed in recent decades. This technology uses light to excite photosensitizer molecules (Photosensitizer, PS) inside cancer cells to generate highly cytotoxic singlet oxygen, which selectively kills cancer cells from the inside of cells, while protecting normal tissues from damage. The principle is to destroy tumors and other pathological tissues through local selective photosensitization of the lesion, that is, to give light of appropriate wavelength to the lesion that has absorbed the photosensitizer, and through the energy or electron transfer mediated by the photosensitizer and oxygen molecules , produce cytotoxic reactive oxygen species (reactive oxy...

Claims

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Application Information

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IPC IPC(8): C08G83/00A61K41/00A61P35/00A61P17/00
CPCA61K41/0071A61P17/00A61P35/00C08G83/008
Inventor 杨洲余兆凤张凯时卓杰何万里王冬曹晖
Owner UNIV OF SCI & TECH BEIJING