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A photosensitive drug sensitive to weak light and preparation method thereof

A photosensitive drug and weak light technology, which is applied in the direction of drug combinations, pharmaceutical formulas, medical preparations of non-active ingredients, etc., can solve the problems of insufficient excitation ability of photosensitizers, limited application range of photodynamic therapy, low light intensity, etc., to achieve Fast speed, high output, and improved effect in hypoxic environment

Active Publication Date: 2019-09-13
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the currently used photosensitizers require strong excitation light irradiation to generate singlet oxygen and thus produce cytotoxicity, and biological tissues have functions such as reflection, absorption and scattering of excitation light, making the light intensity reaching the target tissue relatively low. Low, insufficient excitation ability to photosensitizers, this defect limits the scope of application of photodynamic therapy to a large extent

Method used

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  • A photosensitive drug sensitive to weak light and preparation method thereof
  • A photosensitive drug sensitive to weak light and preparation method thereof
  • A photosensitive drug sensitive to weak light and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The concentration of RB contained in the configuration is 0.01mg·mL under the condition of avoiding light -1 3.5 mL of Hb-RB solution, with 70 μL of 1 mg·mL -1 After the DMSO solution of 9,10-Diphenylanthracene (DPA) was mixed evenly, it was placed in a closed quartz cuvette. Place the cuvette at an intensity of about 50μW / cm 2 Under the weak light irradiation, the absorbance of the system in the range of 350-410nm was measured by a UV-visible spectrophotometer, measured every 5 minutes of irradiation, and the change of the absorbance at 380nm was compared.

[0044] DPA is a commonly used chemical trapping agent, which can quickly react with singlet oxygen to form a stable inner oxide, and the content of singlet oxygen can be measured by measuring the decrease of its absorbance at 380nm. Such as figure 1 As shown, it can be seen that with the prolongation of the irradiation time, the absorbance of the system at 380nm gradually weakens, indicating that the generation ...

Embodiment 2

[0046] Prepare 0.01mg·mL under dark conditions -1 RB solution and the concentration of RB contained in it is 0.01mg·mL -1 Each 1mL of Hb-RB solution was mixed with 20μL of 1mg·mL -1 After the DMSO solution of DPA was mixed evenly, it was placed in a closed micro-quartz cuvette. Use a wavelength of 550nm and a power of 2mW / cm 2 Irradiate the cuvette with the exciting light, measure the absorbance of the system in the range of 350-410nm every minute, and compare the change of the absorbance at 380nm. Such as figure 2 As shown, it can be seen that with the prolongation of the irradiation time, the absorbance at 380 nm in the two systems decreases gradually, and the decrease is more obvious in the Hb-RB system. This phenomenon shows that under the same conditions, the Hb-RB system will generate more singlet oxygen.

Embodiment 3

[0048] Prepare the RB concentration at 0.01mg·mL under dark conditions -1 3.5 mL of Hb-RB solution, with 70 μL of 1 mg·mL - 1 After the DMSO solution of DPA was mixed evenly, it was placed in a quartz cuvette. Nitrogen gas was first introduced to remove the molecular oxygen in the system, and then the system was exposed to indoor visible light conditions (the light intensity was 1.5mW / cm 2 ), feed oxygen, and measure the absorbance of the system in the range of 350-410nm every 5s. Such as image 3 As shown, it can be seen that the absorbance of the solution at 380nm has a significant decrease, that is, the system generates a large amount of singlet oxygen during the process of introducing oxygen, which further indicates that Hb-RB is very sensitive to excitation light, and there are molecules in the system Under the condition of oxygen, it can be excited by ordinary natural light, avoiding the use of high-energy lasers.

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Abstract

The invention discloses a photo-sensitive medicine sensitive to weak light and a preparation method of the photo-sensitive medicine. The photo-sensitive medicine sensitive to weak light is formed by amide condensation reaction of oxygen-carrying protein and a water-soluble sensitizer, wherein the oxygen-carrying protein is hemoglobin or myoglobin; and the water-soluble sensitizer is rose-bengal, photofrin, methylene blueor chlorophyll. The preparation method of the photo-sensitive medicine comprises the following steps of (1) preparing a solution of the photo-sensitive medicine and a solution of the oxygen-carrying protein; (2) sequentially adding a coupling activator and a stabilizer to the solution of the photo-sensitive medicine; and (3) adding the solution of the oxygen-carrying protein to the system in the step (2) and carrying out light-proof stirring reaction to obtain the photo-sensitive medicine. The photo-sensitive medicine has a certain oxygen-carrying function and can be activated under the weak light irradiation condition. Compared with a traditional photo-sensitive medicine, the photo-sensitive medicine disclosed by the invention has the advantages that the speed of generating singlet oxygen is faster after activation, the yield is higher, and the photo-sensitive medicine is expected to be used for photodynamics therapy of internal tissue tumors.

Description

technical field [0001] The invention relates to a photosensitizer and a preparation method thereof, in particular to a photosensitizer sensitive to weak light and a preparation method thereof. Background technique [0002] Photodynamic therapy is a new type of treatment for diseases that has gradually emerged in recent years, and its basis is the photodynamic effect. This luminescence chemical reaction is a photosensitization reaction accompanied by biological effects involving oxygen molecules. The biological tissue is irradiated with excitation light of a specific wavelength (visible light, near-infrared light, ultraviolet light or γ-ray), and the endogenous or exogenous photosensitive substance in it absorbs photon energy and changes from the ground state to the excited state. The photosensitizer in the excited state will quickly transfer energy to the surrounding oxygen molecules, generate highly active singlet oxygen, and undergo oxidation reactions with adjacent bioma...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K47/64A61P35/00
Inventor 李峻柏赵洁
Owner INST OF CHEM CHINESE ACAD OF SCI
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