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Immunologic suppression effect of hydroxycamptothecine and therapeutic effect of hydroxycamptothecine on rheumatoid arthritis

A hydroxycamptothecin, immunosuppressive technology, used in anti-inflammatory agents, bone diseases, non-central analgesics, etc., can solve problems such as adverse reactions in patients

Inactive Publication Date: 2011-02-16
PEOPLES HOSPITAL PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the drugs used to treat such diseases are mainly disease-modifying antirheumatic drugs (DMARDs). Methotrexate and cyclophosphamide, which were initially used as antineoplastic drugs, are also used as immunosuppressants to treat autoimmune diseases, but many patients have adverse reactions. Discontinue due to intolerance

Method used

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  • Immunologic suppression effect of hydroxycamptothecine and therapeutic effect of hydroxycamptothecine on rheumatoid arthritis
  • Immunologic suppression effect of hydroxycamptothecine and therapeutic effect of hydroxycamptothecine on rheumatoid arthritis
  • Immunologic suppression effect of hydroxycamptothecine and therapeutic effect of hydroxycamptothecine on rheumatoid arthritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Embodiment 1: Hydroxycamptothecin treats CIA rats

[0013] 6-week-old female Lewis rats were intradermally immunized with bC II at the base of the tail to establish a CIA model. A total of 36 affected mice were randomly divided into three groups. HCPT 2mg / kg was injected intraperitoneally every day, MTX positive control group 1mg / kg, 1 / week, intraperitoneal injection. At the same time, the normal saline control group was injected intraperitoneally with 200ul, 1 / day. The results of continuous treatment for 4 weeks showed that the body weight of the rats in the three groups showed a steady growth trend during the treatment period, with no significant difference, as shown in Figure 1. Compared with the blank control group, 2mg / kg hydroxycamptothecin treatment can significantly inhibit the joint inflammation of rats, reduce the degree of bone destruction, and significantly reduce the clinical and pathological scores of arthritis, as shown in Figure 2 and Table 1. This s...

Embodiment 2

[0014] Example 2: Effects of Different Concentrations of Hydroxycamptothecin on PBMC Proliferation Inhibition

[0015] Isolation of PBMC from RA patients

[0016] ① Aseptically extract 15-20ml of anticoagulant blood from the patient's vein, and dilute it with PBS buffer. ②Equivalent volume of diluted blood was lightly spread in a 15ml sterile centrifuge tube containing human lymphocyte separation medium, centrifuged at 2000rpm for 20min. ③ Absorb the mononuclear cells in the middle layer, wash them twice with PBS (1500 rpm, centrifuge for 5 min), and discard the supernatant. ④ Mix well with RPMI-1640 culture medium containing 10% FBS.

[0017] The grouping of drugs on cell stimulation

[0018] Dosing in groups: ①Adjust the cell concentration, inoculate in a 96-well culture plate, and spread 2-4×10 cells in each well 5 / ml cell suspension, the total volume of each well is 200μl. Divide cells into negative control group, PHA control group (PHA working concentration is 2 μg / ...

Embodiment 3

[0020] Example 3: The effect of hydroxycamptothecin on PBMC-induced apoptosis and the effect on cell supernatant

[0021] Adjust the cell concentration, inoculate in a 24-well culture plate, and spread 2×10 per well 6 / ml cell suspension, the total volume of each well is 1.5ml. The cells were divided into negative control group, PHA control group, and HCPT stimulation group (working concentration: 1 μg / ml). After 72 hours of culture, the level of TGF-β1 in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA), and Annexin V / PI flow cytometry to detect the effect of HCPT on cell apoptosis.

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Abstract

The invention provides a new medicament hydroxycamptothecine for treating rheumatoid arthritis, which is characterized in that the medicament can inhibit the abnormal immunologic reaction of rheumatoid arthritis so as to control the development of the disease.

Description

technical field [0001] This study involves the immunosuppressive function of hydroxycamptothecin on collagen-induced arthritis (CIA) model and its immunoregulatory effect on peripheral blood mononuclear cells (PBMC) in patients with RA. Application in the treatment of rheumatoid arthritis (RA). Background technique [0002] Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic progressive joint destruction. So far, the cause of the disease is unknown, but the abnormal function of cellular immunity and humoral immunity is the central link of RA autoimmune response. There is a lack of effective drugs and means for the treatment of this disease. At present, the drugs used to treat such diseases are mainly disease-modifying antirheumatic drugs (DMARDs). Methotrexate and cyclophosphamide, which were initially used as antineoplastic drugs, are also used as immunosuppressants to treat autoimmune diseases, but many patients have adverse reactions. Discontinue...

Claims

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Application Information

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IPC IPC(8): A61P37/06A61P29/00A61P19/04A61K31/4745
Inventor 栗占国刘燕鹰郭静
Owner PEOPLES HOSPITAL PEKING UNIV
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