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Applications of (5R)-5-hydroxytriptolide in preparing drugs for treating sepsis

A technology for sepsis and purpose, applied in the field of medicine, can solve the problems of ineffective treatment of organ failure and other problems

Inactive Publication Date: 2020-05-29
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although immunomodulatory drugs can suppress the degree of inflammation in patients to a certain extent by regulating immunity and anti-inflammatory effects, they have little effect on the treatment of organ failure, and even a variety of drugs have been proven to cause MODS, anti-endotoxin antibodies, Attempts to antagonize a single inflammatory mediator and anti-TLR all ended in failure

Method used

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  • Applications of (5R)-5-hydroxytriptolide in preparing drugs for treating sepsis
  • Applications of (5R)-5-hydroxytriptolide in preparing drugs for treating sepsis
  • Applications of (5R)-5-hydroxytriptolide in preparing drugs for treating sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] The preparation of embodiment 1 mouse sepsis model

[0096] A single intraperitoneal injection of lipopolysaccharide (LPS) was used to prepare a sepsis mouse model, and the specific steps were as follows:

[0097] 1. Grouping of mice: 8-12 week-old female C57 mice (with a body weight of about 22-25g, provided by the Animal Experiment Center of Zhongshan Hospital Affiliated to Fudan University) were adaptively fed for one week in an SPF animal room, and the Body weights were randomly grouped to ensure that there was no statistical difference in the average body weight of the mice in each group, and the number of mice in each group was 10.

[0098] 2. Preparation of sepsis mouse model by intraperitoneal injection of lipopolysaccharide: after dissolving lipopolysaccharide (purchased from Sigma) powder with phosphate buffered saline (PBS) (purchased from Sigma), press 6 mg / kg (mg / kg) body weight The ratio of the ratio was intraperitoneally injected into mice to obtain a se...

Embodiment 2

[0099] Mortality investigation after the administration of (5R)-5-hydroxytriptolide in embodiment 2 sepsis mice

[0100] Using a single administration method of oral gavage, (5R)-5-hydroxytriptolide (through compound screening, the sepsis of (5R)-5-hydroxytriptolide) was performed on septic mice. The therapeutic effect is the best and the cytotoxicity is the least, CC50 is 256.6±73.8nM, while other derivatives of Tripterygium wilfordii are <10nM, and the CC50 of triptolide is 2.1±0.2nM, so (5R)-5-hydroxyl triptolide as active ingredient) administration, the specific steps are as follows:

[0101] 1. Grouping of mice: 8-12 week-old female C57 mice (with a body weight of about 22-25g), after being adaptively fed for one week in an SPF animal room, were randomly divided into 5 groups according to the weight of the mice, respectively: Normal mice (blank control, A) sepsis mouse model group (B), sepsis mice plus (5R)-5-hydroxytriptolide low dose (0.125mg / kg) group (C), Sepsis mic...

Embodiment 3

[0106] Example 3 Using (5R)-5-hydroxytriptolide to treat multiple organ injuries in septic mice

[0107] Oral gavage was adopted to administer (5R)-5-hydroxytriptolide in a medium dose (0.25 mg / kg) to septic mice, and normal mice and septic mice were dissected. Select specific tissues and organs for HE staining pathological examination, the specific steps are as follows:

[0108] 1. Grouping of mice: 8-12 week-old female C57 mice (with a body weight of about 22-25g), after being adaptively fed for one week in an SPF animal room, were randomly divided into 3 groups according to the weight of the mice, respectively: Blank control (normal mice) group, sepsis mouse model group, sepsis mice plus (5R)-5-hydroxytriptolide medium dose (0.25mg / kg) group, the number of each group is 10 .

[0109] 2. Prepare (5R)-5-hydroxytriptolide solution: take (5R)-5-hydroxytriptolide powder and dissolve it in PBS containing 0.2% dimethyl sulfoxide (DMSO) to prepare 1mg / ml stock solution and store...

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Abstract

The invention discloses applications of (5R)-5-hydroxytriptolide in preparing drugs for treating sepsis, reducing mortality of the sepsis and / or treating sepsis-related diseases. The drugs can alleviate organic damage to multiple organs and / or abnormal inflammatory response caused by the sepsis, so that the drugs can have wide clinical application prospects.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the use of (5R)-5-hydroxytriptolide in the preparation of medicines for treating sepsis, in particular to the use of (5R)-5-hydroxytriptolide in the preparation of medicines for treating sepsis Use in medicines for treating sepsis, reducing sepsis mortality, and / or treating sepsis-related disorders. Background technique [0002] Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, and its clinical manifestations mainly include severe lung infection, abdominal cavity infection, urinary system infection, bloodstream infection, skin and soft tissue infection, etc. Severe sepsis can be accompanied by complications such as organ dysfunction, tissue hypoperfusion, or hypotension, which can lead to multiple organ dysfunction syndrome (MODS) and even septic shock, which is the most important death in clinical critically ill patients. one of the reasons. Accord...

Claims

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Application Information

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IPC IPC(8): A61K31/585A61K45/06A61P31/00A61P29/00A61P1/16A61P1/00A61P13/12A61P11/00A61P25/00A61P7/00
CPCA61K31/585A61K45/06A61P1/00A61P1/16A61P7/00A61P11/00A61P13/12A61P25/00A61P29/00A61P31/00
Inventor 宋振举杨依霖童朝阳孙湛邝中淑
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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