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Application of kaurane compound in preparation of medicine for preventing and treating inflammatory bowel disease

A technology for inflammatory bowel disease and kauri, which is applied to the application field of kauri compounds in the preparation of medicines for preventing and treating inflammatory bowel disease, and can solve the problems of patient infection, unreported, easy to fail and the like

Active Publication Date: 2021-08-27
KEY PHARMA BIOMEDICAL INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are deficiencies in each of the above drugs. For example, aminosalicylic acid drugs are likely to cause drug resistance in patients, glucocorticoids will relapse after drug withdrawal, and the cost of TNF antibody production and treatment is relatively high. Infection (Paolo Gionchetti, Dig Liver Dis, 2017, 49(6):604-17)
However, compound A and related kaurane compounds have no reports on the above-mentioned immune dysfunction and immune regulation of macrophages and T cells.

Method used

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  • Application of kaurane compound in preparation of medicine for preventing and treating inflammatory bowel disease
  • Application of kaurane compound in preparation of medicine for preventing and treating inflammatory bowel disease
  • Application of kaurane compound in preparation of medicine for preventing and treating inflammatory bowel disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] This case mainly observes the effect of intraperitoneal injection of different doses of compound A on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice.

[0062] Clean grade Balb / c mice, 6-8 weeks old, male. Divide into eight groups at random, establish normal group (give normal saline), model group (free drinking 3.5%DSS), compound A (5mg / kg) blank group, compound A (10mg / kg)+DSS group, compound A (15mg / kg)+DSS group, positive control group 5-ASA(50mg / kg)+DSS group, positive control group Dex(10mg / kg)+DSS group, positive control group IFX(1mg / kg)+DSS group, each group 15 only. After grouping, the mice in the experimental group were intraperitoneally injected with compound A, Dex and IFX, and 5-ASA, and the mice in the control group were injected with normal saline intraperitoneally. The experimental group was administered for 2 consecutive days. From the third day, both the experimental group and the control group began to drink 3.5% DSS aqueous solutio...

Embodiment 2

[0069] This case mainly observes the permeability of the colon of experimental mice in each group.

[0070] 1) Principle: The permeability of animal intestine can be semi-quantitatively detected by using fluorescent tracer to detect the fluorescence intensity in serum.

[0071] 2) Preparation of standard curve:

[0072] Take a few normal mice, collect hemolysis-free serum, weigh 200 μg of FITC-dextran powder, dissolve it in 5ml serum, dilute it in multiples, and then use a microplate reader to detect the fluorescence intensity to obtain a standard curve.

[0073] 3) On the day of sacrificing the animals, fast 4 hours in advance.

[0074] 4) Oral administration of the prepared FITC-dextran tracer at a dose of 60 mg / kg body weight.

[0075] 5) Blood was collected from animals before sacrifice, and serum without hemolysis was collected.

[0076] 6) Serum was added to a 96-well plate, and 100 μl per well was used to detect the fluorescence intensity with a microplate reader (ex...

Embodiment 3

[0080] This case mainly illustrates the effect of compound A on the blood routine of inflammatory bowel disease.

[0081] After the 9th day, blood was collected from the mice, gently dropped into the prepared EP tubes prepared with EDTA salt for anticoagulation, and the 80-100 μL blood samples were mixed evenly, and the blood routine was tested using an automatic blood analyzer, including red blood cell count ( RBC), monocytes (MONO), neutrophils (LYMPH), platelets (PLT), hemoglobin (HGB), hematocrit (HCT) and white blood cell count (WBC), etc.

[0082] Such as Figure 8 As shown, compared with the normal group, the WBC, NEUT, LYMPH and MONO of the model group were significantly increased. After the intervention of compound A, 5-ASA and Infliximab, the WBC, NEUT, LYMPH and MONO all decreased, but the Dex group and the model group There was no significant difference in group comparison.

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Abstract

The invention discloses an application of a kaurane compound in preparation of a medicine for treating inflammatory bowel disease. The kaurane compound can obviously reduce the weight of a dextran sodium sulfate induced (DSS) enteritis model mouse, improve the shortening of the colon length of the colitis model mouse, relieve the infiltration of colon tissue inflammatory cells of the colitis model mouse, reduce the rise of leukocytes, neutrophils, lymphocytes and monocytes of the colitis model mouse, reduce the expression of inflammatory factors, and achieve the immunoregulation function on intestinal tracts. The mechanism of the kaurane compound may be known by adjusting polarization of macrophages and differentiation of T cells, and the kaurane compound can relieve the inflammatory reaction of DSS-induced inflammatory bowel disease model mice and improve the severity of the inflammatory bowel disease, and can be used for preparing drugs or health care products for treating the inflammatory bowel disease.

Description

[0001] field of invention [0002] The invention discloses a kauritanes compound for alleviating and treating inflammatory bowel disease. The invention discloses that the kauritanes compound can obviously reduce the body weight of enteritis model mice induced by dextran sodium sulfate (DSS), improve the shortening of the colon length of the colitis model mice, and reduce the infiltration of inflammatory cells in the colon tissue of the colitis model , reduce the increase of white blood cells, neutrophils, lymphocytes and monocytes in colitis model mice, and reduce the expression of inflammatory factors. The invention discloses the regulating effect of the kauritanes on macrophages and T cells when inflammatory bowel disease occurs. Background technique [0003] Inflammatory bowel disease is a chronic intestinal inflammatory disease with unclear pathogenesis, mainly including ulcerative colitis (Ulcerative Colitis, UC) and Crohn's disease (Crohn's disease, CD). UC is a chroni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/19A61K45/06A61P1/00A61P29/00
CPCA61K31/19A61K45/06A61P1/00A61P29/00Y02A50/30
Inventor 王善平谭文
Owner KEY PHARMA BIOMEDICAL INC
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