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Application of artesunate in the preparation of anti-osteoclast differentiation drugs

A technology of osteoclasts and artesunate, which can be used in drug combinations, bone diseases, and pharmaceutical formulations, and can solve problems such as high prices and osteonecrosis of the jaw

Active Publication Date: 2018-02-02
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most bisphosphonates need to be administered by injection, which is likely to cause serious adverse reactions such as osteonecrosis of the jaw; while denosumab, a biological antibody preparation targeting the osteoclast activating factor RANKL, needs to be administered by subcutaneous injection and is more expensive

Method used

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  • Application of artesunate in the preparation of anti-osteoclast differentiation drugs
  • Application of artesunate in the preparation of anti-osteoclast differentiation drugs
  • Application of artesunate in the preparation of anti-osteoclast differentiation drugs

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0027] Experimental example 1. The cell survival effect of artesunate on RAW264.7 cells:

[0028] RAW264.7 cells 1×10 4 or 1×10 3 Each well was planted in a 96-well plate, and the drug artesunate was added after overnight at a concentration of 3.125 μM, 6.25 μM, and 12.5 μM. 3 replicate wells in each group. After incubating for 8h, 24h, 48h, and 7d respectively, remove the supernatant, add 0.5mg / ml MTT 100μl to each well, incubate in a 37°C incubator for 4h, discard the supernatant, add DMSO 150μl, shake for 10 minutes , Measure the absorbance at 450 nm with a Genios Pro Tecan microplate reader.

[0029] Depend on figure 1 It can be seen that the in vitro concentration ≤ 12.5 μM has no significant effect on the survival of RAW264.7 cells.

experiment example 2

[0030] Experimental example 2. The effect on the differentiation of osteoclast precursor Raw264.7 cells into osteoclasts:

[0031] Select RAW264.7 cells in good growth state and press 1×10 3 Inoculate in a 96-well plate at a density of / ml, and add 100 μl / well of DMEM medium containing 10% FBS, 100 U / ml penicillin G and 100 μg / ml streptomycin, at 37°C, 5% CO 2 Incubator incubation. After the cells were stabilized overnight, in addition to the negative control group (Control group), the positive control group (RANKL group) and the drug group were all added RANKL with a final concentration of 100 ng / ml. 6.25 μM and 12.5 μM (respectively Art1.56 μM group, Art 3.125 μM group, Art 6.25 μM group and Art 12.5 μM group), each group had 3 replicate wells. Change the medium every 2 days. On the 4th day of induction, TRAP staining was observed, photographed under a microscope, and counted as osteoclasts with more than 3 nuclei positive for TRAP. Such as figure 2 .

experiment example 3

[0032] Experimental example 3. Effect on the differentiation of mouse bone marrow macrophages (BMMs) into osteoclasts:

[0033] Take the femur and tibia of C57BL / 6 mice, peel off the muscle and cut off both ends, use a syringe to absorb ice-cold a-MEM and repeatedly wash the bone marrow cavity of the femur and tibia until the bone marrow cavity turns white. %CO 2 After 30 minutes in the incubator, the supernatant suspension was taken. cells by 2 x 10 5 / ml density inoculated in 96-well plate, in addition to the negative control group (Control group), the positive control group (RANKL group) and the drug group were all added M-CSF and RANKL, the final concentration was 50ng / ml, and the drug group was added green Artesunate 1.56 μM, 3.125 μM, 6.25 μM and 12.5 μM (Art1.56 μM group, Art 3.125 μM group, Art 6.25 μM group and Art 12.5 μM group respectively), each group had 3 replicate wells. Change the medium every 2 days. On the 4th day of induction, TRAP staining was observed,...

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Abstract

The invention relates to the application of artesunate in the preparation of anti-osteoclast differentiation drugs. Tests of the present invention have proved that artesunate can directly and significantly inhibit the differentiation of osteoclast precursor cells induced by RANKL in vitro to form osteoclasts, and inhibit osteoclasts from absorbing bone; The bone loss of osteoporotic mice can be significantly improved, and it has the advantages of being convenient to take, economical and effective. Artesunate has the characteristics of direct and significant inhibition of osteoclastogenesis and osteoclast activity, so it can be used as a An osteoclast differentiation inhibitor drug, which is used for diseases treated by osteoclast differentiation inhibitors; as an active drug precursor, it is used in the research and development of osteoclast inhibitor drugs.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a new drug classification application of artesunate. Background technique [0002] The stabilization of bone metabolism requires a dynamic balance and coupling between bone resorption mediated by osteoclasts (OCs) and bone formation mediated by osteoblasts (OBs), which maintain function in healthy individuals Balance, and once the balance is broken, it may lead to the occurrence of bone diseases. [0003] Osteoclasts are the only cells in the body responsible for bone resorption. It can differentiate into functional mature osteoclasts from osteoclast precursor cells after activation. Because differentiated and mature osteoclasts can absorb bone, their excessive activation can cause bone loss, osteoporosis, fracture pain, secondary reactive bone hyperplasia, and even disability. There are many diseases related to the overactivation of osteoclasts. The classic one is postmenopausal osteo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/357A61P19/08A61P19/10
Inventor 李晓娟曾祥周王铿张悦阳陶磊刘叔文
Owner SOUTHERN MEDICAL UNIVERSITY