Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application of pharmaceutical composition

An echinocandin and Candida albicans technology, which can be used in pharmaceutical formulations, antifungal agents, medical preparations containing active ingredients, etc., can solve problems such as inability to effectively inhibit activity, and achieve the effect of treating invasive infections

Active Publication Date: 2020-03-06
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patented medication has two main benefits - it works by killing both yeast fungi (Candidatus) with an antibiotic called Caspofungine or Compound Liang2989, which helps fight off other types of microorganisms like candidemium cysts.

Problems solved by technology

This patent describes various methods aimed towards reducing the risk of developing resistant yeast strains such as AID/Bacillamidium spp., causing opportunist diseases like cryptosporidum meningoencephalitis. One method involves administering different types of medicines called azithromyclin with improved sensory properties compared to other current therapies. Another approach includes modifying the metabolism of certain proteins involved in intracellular growth cycle processes through chemical modifications involving glutathione reductase and cyclooxane dimers. However, there remains room for improvement despite existing chemotherapy options being limited based on its mechanism of action alone.

Method used

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  • Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application of pharmaceutical composition
  • Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application of pharmaceutical composition
  • Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application of pharmaceutical composition

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The chemical structural formula of caspofungin and compound L-269289 is as follows figure 1 As shown, the present embodiment verifies the bactericidal activity of the combined drug to drug-resistant strains through in vitro experiments, and the specific operations are as follows:

[0023] (1) Determination of Candida albicans drug susceptibility test: The determination of Candida albicans drug susceptibility test was completed in a 96-well plate, and 100 ul of yeast extract powder glucose culture solution (YPD) was added to each well. Caspofungin is diluted according to the set concentration (concentration setting see figure 2 A) placed in the well, the designated bacterial strains (wild-type Candida albicans; Candida albicans echinocandin drug-resistant strains, including FKS1 F641S and FKS1 S645F ) was cultured to the logarithmic growth phase, and about 10 3 individual bacteria; measure the strain concentration with a microplate reader after culturing at 30°C in t...

Embodiment 2

[0026] Concentration gradient detection of combined drug: add 100ul of yeast extract powder glucose culture solution (YPD) to each well of 96-well plate, caspofungin and compound L-269289 are diluted according to the set concentration (concentration setting see image 3 ) was placed in the well, and the echinocandin drug-resistant strains of Candida albicans (including FKS1 F641S and FKS1 S645F ) was cultured to the logarithmic growth phase, and about 10 3 individual bacteria; measure the strain concentration with a microplate reader after culturing at 30°C in the dark for 48 hours, and the data are represented by a heat map, such as image 3 shown. image 3 The results showed that: caspofungin used alone at a high concentration of 0.5 μg / ml to 4 μg / ml was effective against echinocandin-resistant strains of Candida albicans, including FKS1 F641S and FKS1S645F The inhibitory effect is weak. However, the combined administration of 1.5μg / ml~4μg / ml caspofungin and 25~35uM L-26...

Embodiment 3

[0028] Toxicity verification of compound L-269289 on human kidney cell line 293, including the following operations:

[0029] (1) The human kidney cell line 293 was provided by the China Center for Type Culture Collection (CCTCC), and was negative for mycoplasma contamination by PCR;

[0030] (2) 293 cells at 5.0×10 per well 4 The concentration of each cell was seeded in a 96-well plate, 10% fetal bovine serum (Everygreen) was added, and DMSO (MP Biomedicine) and compound L-269289 were used, and the concentration was set to 10 μM, 20 μM, 30 μM, 40 μM, and 50 μM. After culturing for 72 hours, Cell counting kit 8 (APExBIO) was used to detect the surviving cells after culture, and the survival rate of cells not treated with L-269289 was set as 100% as a control.

[0031] Experimental results such as Figure 4 As shown in (A), Figure 4 (A) The results show that: L-269289 can inhibit the viability of 293 cells only when the concentration is greater than 40 μM.

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Abstract

The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition for treating invasive infection of candida albicans echinocandin drug-resistant bacteria and an application of the pharmaceutical composition. The active components of the pharmaceutical composition are composed of caspofungin and a compound L-269289, and in a strain for inhibiting drug resistance of candida albicans echinocandin in vitro, the mass ratio of caspofungin to the compound L-269289 is 1: 3-1: 36; and for treating invasive infection of a candida albicans echinocandin drug-resistant strain on mice, and the mass ratio of caspofungin to the compound L-269289 is 1: 10. In-vitro experiments prove that the combined use of caspofungin and the compound L-269289 can effectively killthe candida albicans echinocandin drug-resistant bacteria, and is suitable for treating invasive infection of the candida albicans echinocandin drug-resistant bacteria on mice.

Description

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Claims

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Application Information

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Owner WUHAN UNIV
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