Application of higenamine hydrochloride in preparation of medicine for treating osteoporosis

A technology for higenamine hydrochloride and osteoporosis, which is applied in the field of chemical drug development, can solve the problems of different diseased organs and different pathogenic mechanisms, and achieves the effect of promoting osteogenesis, less side effects, and promoting osteogenic differentiation.

Active Publication Date: 2021-12-24
JINAN CENTER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Myocardial fibrosis and osteoporosis have different types of diseases, different organs, and different

Method used

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  • Application of higenamine hydrochloride in preparation of medicine for treating osteoporosis
  • Application of higenamine hydrochloride in preparation of medicine for treating osteoporosis
  • Application of higenamine hydrochloride in preparation of medicine for treating osteoporosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1: In vivo functional experiment of higenamine hydrochloride

[0048]Experimental method: 12-week-old C57BL / 6J female mice were randomly divided into four groups, namely ovariectomized intragastric administration of PBS solution group (CONTROL group), ovariectomized subcutaneous injection of teriparatide group (T group, the drug solvent was PBS solution), ovariectomized higagenamine hydrochloride group (group H, drug solvent is PBS solution), sham operation group (SHAM group), 10 rats in each group. Inject 3% pentobarbital sodium (35mg / kg) intraperitoneally. After anesthesia, fix on a special animal experiment table in prone position, cut off the local body hair in the operation area, sterilize with iodine, spread sterile towels, and take the back of the mice respectively. The lateral paramedian incision was made, and the bilateral ovaries and fallopian tubes were separated layer by layer. The mice in the CONTROL group, T group, and H group were ligated the ...

Embodiment 2

[0061] Embodiment 2: In vitro functional experiment of higenamine hydrochloride

[0062] experimental method:

[0063] (1) In vitro culture of mouse primary mesenchymal stem cells

[0064] ①Take a 6-8 week old C57 / B6 mouse, remove the mouse femur and tibia after anesthesia, and remove the muscle;

[0065] ②Take autoclaved 300μL and 1.5mL centrifuge tubes, and pierce the bottom of the small tubes;

[0066] ③ Cut off the two ends of the separated lower limb bone, put it in a small tube, add 100 μL of complete medium, and put the small tube in the big tube;

[0067] ④ Centrifuge at 12000rpm, resuspend the cells centrifuged into the large tube, centrifuge at 1000rpm, discard the supernatant, resuspend the cells and seed the plate;

[0068] ⑤After the cell confluence reaches 70%-80%, start the intervention treatment.

[0069] (2) Interfering with the differentiation of mesenchymal stem cells into osteoblasts

[0070] After the cell confluence was 70%-80%, the medium was replac...

Embodiment 3

[0081] Example 3: In vitro pathway verification of higenamine hydrochloride

[0082] Experimental method: Take mouse osteoblast precursor cells MC3T3-E1 in the logarithmic growth phase, inoculate them into 6-well plates, and place them at 37°C and 5% CO 2 In the incubator with saturated humidity, when the culture medium (a-MEM, 10% FBS, 1% double antibody) was used to culture the cells to grow to 70%-80%, the CONTROL group was given DMSO, and the T group was given TGF-β protein (drug The solvent was DMSO, with a final concentration of 10 ng / mL), and group H was given higenamine hydrochloride (the drug solvent was DMSO, and the final concentrations of samples used for Western Blot detection were 0.08, 0.4, 2, 10, 50, and 250 μM, respectively, with The final concentration of the sample detected by immunofluorescence was 10 μM), placed in the incubator for 6 hours, and the relevant indicators of the TGF-β pathway were detected by Western Blot and immunofluorescence.

[0083] Det...

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Abstract

The invention relates to application of higenamine hydrochloride in preparation of a medicine for treating osteoporosis, and belongs to the technical field of chemical medicine development. It is found for the first time that higenamine hydrochloride can activate a Smad2/3 pathway and promote Smad2/3 phosphorylation by targeting IQGAP1 protein, so that osteogenic differentiation is promoted, and the higenamine hydrochloride has the potential to become a new medicine for treating osteoporosis. At present, the osteoporosis is clinically treated mainly by anti-bone resorption medicines such as diphosphates and the like, however, with different causes and development of disease courses of the osteoporosis, pure anti-bone resorption cannot meet the requirements of patients, while the unique osteogenesis promoting medicine teriparatide has long-term osteosarcoma risk and other side effects and limitations; and the higenamine hydrochloride has the characteristics of oral administration and injection, small side effect, obvious osteogenesis promoting effect and the like, and provides a new choice for clinical treatment of osteoporosis.

Description

technical field [0001] The invention relates to the application of higenamine hydrochloride in the preparation of medicines for treating osteoporosis, and belongs to the technical field of chemical medicine development. Background technique [0002] Osteoporosis is a systemic and degenerative disease of the skeletal system, characterized by damage to the bone microstructure and decreased bone mass, leading to muscle weakness, decreased bone strength, increased bone fragility, and increased risk of fracture. characteristic metabolic disease. With the acceleration of population aging, the current prevalence rates of low bone mass and osteoporosis over the age of 50 in my country are 46.4% and 19.2%, respectively, and the cost of diagnosis and treatment is huge. [0003] Bone is seamlessly created and replaced in a dynamic process called bone remodeling. Bone remodeling consists of two sequential phases: osteoclastic bone resorption and osteoblastic bone formation. These two...

Claims

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Application Information

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IPC IPC(8): A61K31/472A61P19/10A23L33/105
CPCA61K31/472A61P19/10A23L33/105A23V2002/00A23V2200/306A23V2250/21
Inventor 宁斌董辉刘镕菡金政鑫张英邹珂
Owner JINAN CENTER HOSPITAL
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