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Application of cyclodextrins to treatment and/or prevention of sepsis

A sepsis and cyclodextrin technology, applied in the field of medicine and biology, to achieve the effects of low cytotoxicity, increased mortality, and strong binding effect

Active Publication Date: 2017-12-22
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The most notable feature of the CDs structure is that it has a stereochiral cavity with a hydrophilic outer ring and a hydrophobic inner ring with a certain size, while LPS has a hydrophilic region anion (phosphate group) and a hydrophobic region (5-7 hydrophilic In the natural state, LPS has the characteristics of self-assembly to form molecules with larger molecular weight. Based on this property, the therapeutic effect of CDs in vivo is developed, and the hydrophobic cavity of CDs can be used to contain and class The role of the hydrophobic chain of lipid A to block the role of LPS as the initiating factor of the inflammatory storm in sepsis, the way of antibiotics combined with CDs in the treatment of sepsis has not been reported

Method used

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  • Application of cyclodextrins to treatment and/or prevention of sepsis
  • Application of cyclodextrins to treatment and/or prevention of sepsis
  • Application of cyclodextrins to treatment and/or prevention of sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 The inhibitory effect of five CDs on the binding of LPS to macrophages and the effect on the activity of macrophages

[0061] 1. Detection of the inhibitory effect of five CDs on the binding of LPS to macrophages by confocal laser microscopy

[0062] The experiment was divided into blank group, LPS control group and five CDs administration groups including α-CD, β-CD, γ-CD, HP-β-CD and β-CD-polymer.

[0063] RAM264.7 cells in the logarithmic phase were taken, digested with trypsin and centrifuged, discarded the supernatant, added DMEM medium containing 10% fetal bovine serum to make a cell suspension, and counted on a cell counting plate. Cells were plated in laser confocal small dishes (2×10 5 / dish cells), then placed at 37°C, 5% CO 2 Cultivate in the incubator for 24 hours, discard the medium, and add PBS to wash three times. The blank group did not receive any drug intervention; the LPS group added FITC-LPS with a final concentration of 100ng / ml to stim...

Embodiment 2

[0070] Example 2 The therapeutic effect of five CDs on sepsis

[0071] 1. Effects of five CDs on the survival rate of septic mice modeled with LPS

[0072] Experimental grouping: The experiment was divided into LPS control group and five CDs administration groups of α-CD, β-CD, γ-CD, HP-β-CD and β-CD-polymer.

[0073] Experimental method: BALB / c mice were randomly divided into six groups according to the digital method, with 7 mice in each group. Mice in the LPS control group were intraperitoneally injected with LPS (20 mg / kg) as a model for the survival rate of sepsis mice. α-CD, β-CD, γ-CD, HP-β-CD and β-CD-polymer five CDs administration group were intraperitoneally injected with 20mg / kg LPS and 100mM or 50mM CDs mixed solution. After modeling, the mice in each group were raised normally in the laboratory, and the death of the mice was observed and recorded within 60 hours.

[0074] The survival rate of mice in each group within 60h is as follows: Figure 4 shown by F...

Embodiment 3

[0082] Example 3 The therapeutic effect of γ-CD and HP-β-CD combined with antibiotics on septic mice

[0083] 1. Establishment of a sepsis model in CLP mice

[0084] Select KM mice, inject 4% chloral hydrate (0.1ml / 10g) into its right lower abdomen for anesthesia, fix the limbs and tail of the mice on the operating table with medical adhesive tape, and make the abdomen face up. Disinfect the abdominal skin of the mouse with iodine, use scissors to make a longitudinal incision about 0.5-1 cm long parallel to the midline at a position about 0.2-0.5 cm to the left of the xiphoid process, expose the cecum, separate the cecum, and use 4- 0. The surgical line is ligated about 1cm from the end of the cecum. At the midpoint of the ligated cecum, use a 18-gauge puncture needle to puncture twice. , Put the cecum back into the abdominal cavity, and pay attention to avoid the extruded feces touching the surgical wound. After disinfecting the incision, the abdomen was closed layer by lay...

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Abstract

The invention discloses application of cyclodextrins to treatment and / or prevention of sepsis and discovers novel pharmacologic actions of CDs commonly used as pharmaceutic adjuvants. The novel pharmacologic actions of CDs are the effects of preventing and / or treating sepsis. Through detection through a laser confocal fluorescence microscope and an MTT method, the invention discovers that CDs can prevent combination of LPS and mouse peritoneal macrophages and are free of obvious cytotoxicity; five CDs have no effect of treating sepsis under high concentration, but gamma-CD and HP-beta-CD have good effects of treating sepsis under low concentration; the combination medication of gamma-CD, HP-beta-CD and antibiotics has an obvious treatment effect on mice with sepsis, can effectively reduce the death rate of the mice, and has great significance in prevention and treatment of sepsis.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and relates to the application of cyclodextrin in the prevention and / or treatment of sepsis caused by bacterial infection, especially the application of γ-CD or HP-β-CD in the treatment and / or prevention of sepsis . Background technique [0002] Sepsis refers to the systemic inflammatory response syndrome (SIRS) caused by infection. Sepsis is a serious life-threatening disease and an important cause of death for patients in the Intensive Care Unit (ICU). Sepsis is mainly caused by infectious agents, such as Gram-positive (G + ) bacteria, Gram-negative (G - It is caused by the invasion of pathogenic microorganisms such as bacteria, fungi, and viruses. Its clinical manifestations include primary infection lesions, systemic inflammatory responses, respiratory system, cardiovascular system, liver and other organ functions and metabolic changes. Sepsis has a mortality rate as high as 30% to 70%...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/724A61K45/06A61P31/04
CPCA61K31/724A61K45/06
Inventor 崔慧斐高雪
Owner SHANDONG UNIV
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