Application of pentamer lysinephthalocyanine zinc in killing staphylococcus aureus

A pentalysine zinc phthalocyanine and drug technology, which is applied in the direction of antibacterial drugs, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problem of short excitation wavelength of photosensitizers, expensive photosensitizers, and tissue penetration Poor compatibility and other problems, to achieve the effect of good water solubility, high specificity, and simple preparation

Inactive Publication Date: 2012-10-31
FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although these photosensitizers have been improved and developed in recent years, they still have some disadvantages, such as: photosensitizers extracted from natural products are more expensive; photosensitizers with shorter excitation wavelengths (ketovaleric acids and porphyrins) and thus have poor tissue penetration; some photosensitizers are mixtures and lack defined structures

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1 Preparation of pentameric lysine phthalocyanine zinc compound

[0015] The synthesis of the compound includes the following steps: in the presence of coupling agent N,N-dicyclohexylcarbodiimide and activator 1-hydroxybenzotriazole, the carboxyl functional group on the 2-monocarboxyl substituted zinc phthalocyanine is activated 30 minutes. Add the pentalysine resin with exposed N-terminal, stir at room temperature for 12 hours, wash the reacted resin with N,N-dimethylformamide until the filtrate is colorless, wash with methanol several times, freeze Dry and ready to use. Take the above freeze-dried sample and add 95% TFA to peel off the pentalysine zinc phthalocyanine from the resin. After washing the resin for 2-3 times, filter it, add anhydrous ether to precipitate solid pentalysine phthalocyanine zinc, and freeze-dry it into powder.

Embodiment 2

[0016] Example 2 Quantitative killing of Staphylococcus aureus by pentalysine zinc phthalocyanine

[0017] Preparation of bacterial propagule suspension: take the glycerin strain tube, open it under aseptic operation, take a test tube containing 2 ml of nutrient broth medium, drop a little strain suspension, and incubate at 37°C for 18 hours to prepare the bacteria Suspension, first use the bacterial concentration turbidimetric assay to roughly measure its bacterial concentration, and then dilute it with phosphate buffer to the required concentration of 1×10 8 cfu / ml.

[0018] Prepare gradient solution of pentalysine zinc phthalocyanine fungicide (in terms of molar concentration of pentalysine zinc phthalocyanine): 200 μM, 100 μM, 50 μM, 25 μM, 12.5 μM, 6.25 μM, all use polyoxygen Ethylene castor oil, pH 7.4 phosphate buffer solution, put in a water bath at 20℃±1℃ for later use.

[0019] Take a sterile 1.5ml EP tube, first add 0.18ml of the test bacterial suspension, and use...

Embodiment 3

[0023] Example 3 Injury experiment of pentalysine zinc phthalocyanine on human embryonic lung fibroblasts

[0024] After the human embryonic lung fibroblasts were digested with 0.25% trypsin, the culture medium was used to make a cell suspension, and 200 μl of the cell suspension was added to each well of a 96-well culture plate, about 10,000 cells. Move the culture plate into a 37°C incubator and let it stand overnight, then add fungicides so that the final concentrations (based on the molar concentration of pentalysine phthalocyanine zinc) are: 20 μM, 10 μM, 5 μM, 2.5 μM, 1.25 μM , move the culture plate into a 37°C incubator and incubate in the dark for 2 hours, then irradiate it with an LED light source with a wavelength of 670nm and a power of 100mW for 2 minutes, then move it into a 37°C incubator and culture it for 1 day, discard the medium, and wash each well Add 200 μl of RP1640 medium containing MTT (0.5 mg / ml), move into a 37° C. incubator and continue to incubate f...

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PUM

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Abstract

The invention relates to an application of pentamer lysinephthalocyanine zinc in killing staphylococcus aureus. The pentamer lysinephthalocyanine zinc are taken as the main component for killing staphylococcus, and a phosphate buffer solution and a medical surfactant are added as auxiliary agents to prepare a drug for killing staphylococcus aureus. The drug has the advantages that the main component has a definite structure with the purity reaching more than 98 percent, and has a good water solubility; the drug can be specially combined with cell membranes of bacteria, is low in use concentration, and has small toxicity on human embryonic lung fibroblast and skin; and when the concentration of the pentamer lysinephthalocyanine zinc is greater than 5 mu M, as long as a light source with excitation wavelength of 670 nm is used to radiate for 2 minutes, more than 99.99 percent of staphylococcus aureus can be killed. Thepentamer lysinephthalocyanine zinc has a good application prospect.

Description

technical field [0001] The invention relates to the application of pentameric lysine zinc phthalocyanine in the preparation of drugs for killing Staphylococcus aureus. Background technique [0002] The genus Staphylococcus includes at least 20 species, among which Staphylococcus aureus is an important pathogenic bacterium of humans and can cause a variety of serious infections. The sterilization methods mainly include: filter sterilization, ultraviolet sterilization, microwave sterilization, Radiation sterilization and chemical sterilization, etc. Most of the above methods have certain defects, and damage to the human body and active substances to a certain extent. The lack of effective and selective sterilization methods is still the bottleneck of killing Staphylococcus aureus technology. [0003] Photodynamic sterilization is a method developed in recent years to kill pathogenic bacteria. This method mainly uses singlet oxygen produced by the interaction of appropriate li...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K31/409A61P31/04
Inventor 黄明东周山勇胡萍陈锦灿陈卓
Owner FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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