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Application of paeoniflorin derivative CP-25

A technology of CP-25 and derivatives, applied in the field of known compounds, can solve the problems of unsatisfactory treatment effect and unclear mechanism of glioma, and achieve the effect of improving bioavailability and stable properties

Inactive Publication Date: 2019-03-19
ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, anti-angiogenesis therapy has excellent results in clinical studies of other tumors, but the effect in glioma treatment is not satisfactory; including bevacizumab to block VEGF, vatalanib or cediranib to inhibit VEGF receptor [9], this phenomenon is not yet well explained
In addition, some immunomodulators, such as thalidomide and lenalidomide, also showed certain curative effect on glioma [9], but the mechanism is still unclear

Method used

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  • Application of paeoniflorin derivative CP-25
  • Application of paeoniflorin derivative CP-25
  • Application of paeoniflorin derivative CP-25

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0032] Experimental example 1: The compound of the present invention inhibits the tumorigenesis of glioma ectopic tumorigenesis model in nude mice

[0033] In order to confirm the inhibitory effect of CP-25 on tumorigenesis in vivo, GL261 cells (a mouse-derived glioma cell line) were used to carry out xenograft tumor models in nude mice (subcutaneous injection of 1x10 6 cells / only). 30 nude mice, male, weighing 20±2g. Experimental animals were randomly divided into 3 groups, namely: model group, positive control group (TMZ, 25 mg·kg -1 ), CP-25 administration group (50mg·kg -1 ). Medication regimen: From 2 days before modeling, different doses of drugs were given by intragastric administration according to the volume of 0.1ml / 10g, once a day, for 21 consecutive days. The normal group and the model group were given corresponding volumes of CMC-Na. The experimental results See figure 1 .

[0034] Administration of CP-25 resulted in an apparent inhibitory response to xenogr...

experiment example 2

[0035] Experimental example 2: The compound of the present invention inhibits the tumor formation of glioma brain orthotopic PDX model in nude mice

[0036] In addition, the antitumor effect of CP-25 on glioma in vivo was further verified using a patient-derived xenograft model. Tumor cells were isolated by cell sorting from glioma patients and injected directly into the brains of nude mice (1x10 5 cells / 5uL / only)( figure 2 A). In this experiment, 30 nude mice, male, weighing 20±2g were used. Experimental animals were randomly divided into 4 groups: normal group, model group, positive control group (TMZ, 25mg·kg -1 ), CP-25 group (50mg·kg -1 ). Medication regimen: From 2 days before modeling, different doses of drugs were given by intragastric administration according to the volume of 0.1ml / 10g, once a day, for 21 consecutive days. The normal group and the model group were given corresponding volumes of CMC-Na.

[0037] CP-25 treatment significantly prolongs the surviva...

experiment example 3

[0038] Experimental example 3: In vitro cytological inhibitory activity of the compound of the present invention

[0039] Proliferation and migration assays were performed in primary glioma tumor cells, the mouse glioma cell line GL261 and the human glioma cell line T98G. However, CP-25 treatment did not directly affect the proliferation and migration of primary glioma cells, GL261 and T98G cells. CP-25 has been shown to be an immunomodulator in a range of autoimmune diseases. Therefore, we speculate that CP-25 may affect glioma cells by regulating immune cells in the tumor microenvironment. Macrophages are the most abundant immune cells in tumor tissues. We isolated glioma tumor-associated macrophages from glioma tissues and co-cultured with primary glioma cells by using a transwell co-culture chamber ( image 3 A). The proliferation of primary glioma tumor cells was inhibited by co-culture with CP-25-treated TAMs ( image 3 B). Similar results were produced in GL261 and...

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Abstract

The invention discloses application of a paeoniflorin derivative CP-25. The application refers to application in preparation of a pharmaceutical preparation for treating human brain glioma. The structural formula of the paeoniflorin derivative CP-25 is as shown in the specification. The paeoniflorin derivative CP-25 disclsoed by the invention is capable of achieving an effect of inhibiting gliomaoccurrence and development by inhibiting tumor-associated macrophage mediated angiogenesis, and can be prepared into injection, tablets, capsules, dropping pills, granules and the like.

Description

technical field [0001] The present invention relates to the use of a known compound, in particular to the use of a paeoniflorin derivative CP-25. Background technique [0002] Human glioma is the most common tumor of the central nervous system, accounting for about 3% of all malignant tumors and 40%-50% of adult intracranial tumors [1]. Glioma is an infiltrating growth tumor with no obvious boundary with normal brain tissue. It is usually not limited to one lobe of the brain. The average time from symptoms to treatment is two years. The malignant tumors grow rapidly and the course of disease is short. Most of them are within 3 months from the onset of symptoms to the time of treatment, and 70-80% are within half a year. Glioma is the malignant tumor with the highest incidence rate in China. It is difficult to remove completely by surgery, and the recurrence rate and mortality are high. At present, surgery is mainly used in clinical practice, supplemented by radiotherapy, ch...

Claims

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Application Information

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IPC IPC(8): A61K31/7048A61P35/00
CPCA61K31/7048A61P35/00
Inventor 魏伟涂佳杰
Owner ANHUI MEDICAL UNIV
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