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Application of calcipotriol as skin external medicine for preventing and treating senile osteoporosis

A technology of calcipotriol and osteoporosis, which is applied in the field of anti-osteoporosis-related drugs to achieve drug safety, promote the formation of osteoblasts and osteoclasts, and increase bone formation

Pending Publication Date: 2021-07-30
黄彬
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Most of the existing anti-osteoporosis drugs are taken orally, and a small part is administered intravenously. At present, there is no anti-osteoporosis drug for external use on the skin

Method used

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  • Application of calcipotriol as skin external medicine for preventing and treating senile osteoporosis
  • Application of calcipotriol as skin external medicine for preventing and treating senile osteoporosis
  • Application of calcipotriol as skin external medicine for preventing and treating senile osteoporosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Decreased expression and secretion of CSTA in the skin of aged osteoporotic patients and mice

[0040] According to the clinical phenomenon of "skin thinning in elderly patients with osteoporosis", the inventors believed that the skin may enter the bone through secreted factors and affect the occurrence of osteoporosis in the elderly. In order to discover and identify the skin-secreted factors that lead to senile osteoporosis, the inventors conducted a protein profile screening analysis on the skin tissues of 3 pairs of old and young mice.

[0041] Specific process: Take an appropriate amount of skin tissue samples into a mortar pre-cooled with liquid nitrogen, add liquid nitrogen to fully grind to powder. Each group of samples was added with 4 times the volume of powdered lysis buffer (1% TritonX-100, 1% protease inhibitor) and ultrasonically lysed. Centrifuge at 12,000 g for 10 min at 4°C to remove cell debris, transfer the supernatant to a new centrifuge tube, and u...

Embodiment 2

[0049] Reduced secretion of CSTA by skin keratinocytes leads to senile osteoporosis.

[0050] The inventor then constructed a mouse model of skin keratinocyte-specific CSTA gene knockout, used micro-CT to detect bone mass changes in the lower limbs of mice, and performed pathological analysis on mouse bone sections to verify whether the reduction of skin CSTA leads to senile bone loss. quality loose.

[0051] Specific method: After the mice were sacrificed, the hind limbs were cut off (the femur and tibia remained intact), the surrounding muscle tissue was carefully removed, and the complete bone tissue was fixed in absolute ethanol for 48 hours. Ex vivo micro-CT scans were performed on the right distal femurs of mice in the control group and CSTA knockout group (n=5). The micro-CT used was VivaCT40 (Scanco Medical AG, Bassersdorf, Switzerland). Scans were started from the lower growth plate and extended 300 slices proximally at a resolution of 12 μM. Morphometric analysis ...

Embodiment 3

[0060] Calcipotriol applied externally to the skin treats senile osteoporosis in mice by increasing the secretion of CSTA from keratinocytes

[0061] Taking mice as an example, it was verified that calcipotriol applied externally to the skin can be used to prevent and treat senile osteoporosis. Specific process: the mice were divided into 3 groups (all aged mice aged 18 months): normal C57 mice (control group), normal C57 mice skin smeared with calcipotriol (calcipotriol group), cutin Calcipotriol was applied to the skin of the cell-knockout CSTA mice (calcipotriol+CSTA knockout group). The hair in the 4cm*2cm region of the back skin of the mice was shaved, 75% ethanol was applied to the control group, and calcipotriol working solution (concentration: 22.5uM) was applied to the skin surface of the other two groups. Apply once a day for 2 months. 22.5uM calcipotriol working solution preparation method: dissolve 1mg MC903, Tocris, MM=412.6g / mol in 5.386ml ethanol. This stock ...

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Abstract

The invention provides application of calcipotriol as a skin external medicine for preventing and treating senile osteoporosis. Along with aggravation of population aging, senile osteoporosis patients are increasingly increased, and huge social, medical and economic burdens are brought to the whole world. Existing anti-osteoporosis drugs are not ideal in treatment effect on senile osteoporosis and have different degrees of side effects. Through in-vivo and in-vitro experiments and preliminary clinical curative effect observation, it is found that external calcipotriol for skin can increase expression and secretion of skin keratinocyte CSTA, after CSTA enters bones through blood circulation, formation of osteoblasts and osteoclasts is promoted at the same time, the bone conversion rate is increased, bone formation is increased, and therefore senile osteoporosis is prevented and treated. The calcipotriol is less in percutaneous absorption and short in half-life period, and main metabolites have no pharmacological activity. The calcipotriol for external use on the skin has no obvious side effect and is high in safety coefficient. The invention provides the application of the medicine for preventing and treating senile osteoporosis by adopting a skin external application mode, and the medicine is safe to use.

Description

technical field [0001] The invention relates to the technical field of drugs related to anti-osteoporosis, in particular to the use of calcipotriol as an external skin drug for preventing and treating senile osteoporosis. Background technique [0002] Bone is constantly renewed and regenerated through bone turnover, replacing old bone with multiple fatigue microfractures with new bone to maintain the integrity of bone structure and mechanics. Bone turnover is mainly accomplished by osteoblasts responsible for bone formation and osteoclasts responsible for bone resorption. Before the age of 30, bone formation dominates until peak bone mass is reached. Between 30 and 50 years old, bone formation and bone resorption are generally balanced, and bone mass is basically constant. In old age, this balance shifts in a negative direction (bone formation < bone resorption) and leads to osteoporosis. [0003] Osteoporosis (Osteoporosis, OP) is a systemic metabolic bone disease, ch...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/593A61P19/10
CPCA61K31/593A61K9/0014A61P19/10
Inventor 黄彬陈庆靖梁文全魏锐铭姚晨丰欧阳志聪刘则征
Owner 黄彬
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