Application of chloroquine or derivative hydroxychloroquine

A derivative, the technology of hydroxychloroquine, applied in the field of biomedicine, can solve the problems of high price, limited wide application, and limited drugs, and achieve the effect of low price, saving social resources, and high safety

Pending Publication Date: 2020-01-03
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the effective rate of clinical application of glucocorticoids is 63% (oral) to 88% (venous pulse), but it is often only for acute or moderately severe patients, and it cannot reverse the infiltrating exophthalmos of GO, and the side effects such as edema, obesity, bone Its application is also limited due to osteoporosis, and surgery and radiation therapy are only used as supplementary treatments. Therefore, it is urgent to explore new treatment strategies for the etiology[1,2]
Orbital fibroblasts (OFs) excessively pr...

Method used

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  • Application of chloroquine or derivative hydroxychloroquine
  • Application of chloroquine or derivative hydroxychloroquine
  • Application of chloroquine or derivative hydroxychloroquine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Chloroquine and its derivative hydroxychloroquine inhibit the proliferation of OFs in patients with GO

[0030] Method steps:

[0031] A) OFs from GO patients (n=6) were extracted and passaged to P2 in proliferation medium for experiments. They were divided into chloroquine group (0, 0.5, 1, 5, 10, 25, 50, 100 μM) and hydroxychloroquine group (0, 0.5, 1, 5, 10, 25, 50, 100 μM) , 0.5, 1, 5, 10, 25, 50, 100 μM), after starting the treatment, add the same concentration of CCK8 for 3 consecutive days and read the absorbance (450 nm) after culturing for 4 h. As the concentration of chloroquine or hydroxychloroquine increases and the action time is prolonged, Cell viability gradually decreased; B) OFs (n=6) from GO patients were extracted, passaged to P2 in proliferation medium for experiments, and divided into hydroxychloroquine groups (0, 0.5, 1, 5, 10, 25, 50, 100 μM) , after starting the treatment, adding the same concentration of CCK8 for 3 consecutive days an...

Embodiment 2

[0035] Example 2: Chloroquine and its derivative hydroxychloroquine inhibit the adipogenic differentiation of OFs in GO patients

[0036] Method steps:

[0037] A) The OFs (n=3) of GO patients were taken and passaged to P3 in the proliferation medium. When the cell density reached more than 90%, the induction medium was switched to. They were divided into the control group, the chloroquine group (10 μM) and the hydroxychloroquine group ( 5μM) in 3 groups in total, cells were fixed after 10 days, and normal phase contrast images and images after Oil Red O staining were taken with an optical microscope (100×).

[0038] B) After 4 days of successful induction and differentiation, the cells of each group were collected to extract RNA, and real-time quantitative PCR was performed to detect the changes of markers related to adipogenic differentiation.

[0039] result:

[0040] The exophthalmos of GO patients are mainly caused by the adipogenic differentiation of OFs compressing th...

Embodiment 3

[0042]Example 3: Chloroquine inhibits the synthesis and secretion of hyaluronic acid in OFs in GO patients

[0043] Method steps:

[0044] The OFs (n=4) of GO patients were taken and passaged in the proliferation medium to P3 for experiments. They were divided into IL-1β-treated group and non-treated group, and further divided into control group, chloroquine group (10 μM) and hydroxychloroquine group (5 μM). ) A total of 3 groups, treated cells for 48 hours, took the supernatant of the medium, centrifuged at 4°C to remove dead cells, and used a hyaluronic acid enzyme-linked immunosorbent assay (Enzyme-linked immunosorbent assay, ELISA) kit to detect the hyaluronic acid concentration. Cells were used to extract RNA to detect HAS2 expression.

[0045] result:

[0046] Hyaluronic acid is the main hydrophilic mucopolysaccharide in the orbit of GO patients, which promotes the increase of periorbital contents and compresses surrounding tissues, and its secretion is significantly i...

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Abstract

The invention belongs to the technical field of biomedicine, and relates to new application of chloroquine or a derivative hydroxychloroquine medicine, in particular to application of chloroquine or derivative hydroxychloroquine in medicine for treating Graves eye diseases. The invention proves that the chloroquine or the derivative hydroxychloroquine thereof has an obvious inhibition effect on excessive proliferation, adipogenic differentiation and hyaluronic acid synthesis of fibroblasts; the effects are superposed to show that: the chloroquine and the derivative hydroxychloroquine thereof can effectively regulate and control the pathology dominant factor of Graves eye disease, namely, fibroblast pathophysiology; and the invention indicates that the chloroquine and the derivative hydroxychloroquine thereof have potential treatment value on Graves eye diseases from the pathophysiological level, and the chloroquine and a new medicine application is provided, so that social and scientific research resources can be saved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a new use of chloroquine or derivative hydroxychloroquine medicine, more particularly, to the use of a kind of chloroquine or derivative hydroxychloroquine in medicine for treating Graves ophthalmopathy. Background technique [0002] Chloroquine (CQ) has been used clinically since 1944; it was initially used to treat malaria, and its use was gradually expanded later. In 1951, it was used to treat chloroquine rheumatoid arthritis, with certain effects. [0003] Graves ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves disease, accounting for about 50%, manifesting as eyelid contracture, proptosis, pain, redness, and even optic nerve compression, causing blindness, and seriously affecting the health and quality of life of patients . At present, the effective rate of clinical application of glucocorticoids is 63% (oral) to 88% (intravenous pulse), but ...

Claims

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Application Information

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IPC IPC(8): A61K31/4706A61P27/02
CPCA61K31/4706A61P27/02
Inventor 李延兵郭衍李海陈雪莹陈雨馨管洪宇刘烈华肖海鹏
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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