Nano-drug for treating osteoporosis as well as preparation method and application of nano-drug

A technology for osteoporosis and nano-drugs, applied in nano-drugs, drug combinations, drug delivery, etc., can solve the problem of reducing the rapid blood clearance rate of NDDS and achieve good dispersion performance

Active Publication Date: 2022-03-04
PEKING UNIV SCHOOL OF STOMATOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This is also a key issue that currently prevents NDDS from being put into clinical application. It can significantly reduce the rapid blood clearance rate of NDDS.
So far, the applicant has not found any literature reports on the combination of DNA aptamers and nanomaterials for OP treatment

Method used

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  • Nano-drug for treating osteoporosis as well as preparation method and application of nano-drug
  • Nano-drug for treating osteoporosis as well as preparation method and application of nano-drug
  • Nano-drug for treating osteoporosis as well as preparation method and application of nano-drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1. Preparation method of mesoporous silica nano-medicine with deliberate targeting of bone tissue and therapeutic efficacy of osteoporosis

[0051] Including the following steps:

[0052] 1) After mixing 48ml of 25% cetyltrimethylammonium chloride (CTAC) solution with 72ml of deionized water, add 0.36g of triethanolamine (TEA) as a catalyst, under 60 ℃ oil bath heating condition Maintain for one hour, wait for the CTAC micelles to self-assemble into a template; mix tetraethyl orthosilicate (TEOS) into cyclohexane at a ratio of 20% (v / v), use a latex dropper to draw 20ml and add the above CTAC and TEA Among the reactants, an upper layer oil phase solution and a lower layer water phase solution are formed. After continuous stirring at a low speed for three hours under the condition of 60°C oil bath heating, the aqueous layer solution will gradually turn into light milky white. After using a separatory funnel to obtain the aqueous phase liquid, filter out the imp...

Embodiment 2

[0059] Embodiment 2, DNAM protection Aptscl56 experiment

[0060] Configuration concentration is the PBS solution of the DNA degrading enzyme I of 50ug / ml, add the free Aptscl56 of 500nmol and the DNAM containing 500nmol Aptscl56 respectively, observe the degradation situation of Aptscl56 by the method of DNA level electrophoresis at 0.25, 0.5, 2 and 24 hours respectively, The result is as figure 2 as shown ( figure 2 ). From figure 2 It can be seen that DNAM can well protect its surface Aptscl56 from being destroyed. In contrast, free Aptscl56 was rapidly degraded by DNA-degrading enzyme I and was almost completely degraded at 24 hours.

Embodiment 3

[0061] Embodiment 3, animal experiment 1

[0062] 20 nmol of free cy3-Aptscl56 (provided by Suzhou Beixin Biotechnology Co., Ltd.), 400 μg carrier PEGM and 400 μg nanomedicine DNAM modified by cy3-fluorescence at the 5’ end were injected into healthy mice through the tail vein. Each 100 μg of DNAM surface contained 5 nmol of Aptscl56 molecules. The experimental animals were sacrificed 1 hour, 12 hours, 1 day and 7 days after the injection, and the heart, liver, spleen, lung, bilateral kidneys, femur and tibia were collected, and the above specimens were scanned, qualitatively and qualitatively analyzed using a living fluorescence scanner. Quantitative analysis, see the results image 3 . Such as image 3 As shown in the histogram, DNA aptamers can specifically attach DNAM to the surface of bone matrix, and compared with free DNA aptamers and PEGM, its attachment time is longer, which can achieve long-term therapeutic effects.

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Abstract

The invention discloses a nano-drug for treating osteoporosis and a preparation method and application of the nano-drug. The nano-drug comprises a DNA (deoxyribonucleic acid) aptamer Aptscl56 and PEG (polyethylene glycol) functionalized mesoporous silica nanoparticles, and the nano-drug disclosed by the invention is obtained by grafting the DNA aptamer on the PEG functionalized mesoporous silica nanoparticles. The nano-drug disclosed by the invention can be specifically targeted to bone tissues and can effectively neutralize osteosclerosis protein in a bone tissue environment, so that the effect of efficiently treating osteoporosis is achieved.

Description

technical field [0001] The present application relates to the field of molecular biomedicine, in particular, to a nano-medicine for treating osteoporosis and its preparation method and application. Background technique [0002] Osteoporosis (Osteoporosis, OP) is a systemic skeletal disease characterized by low bone mineral density (bone mineral density, BMD) and microarchitectural degeneration of bone tissue, which increases bone fragility and fracture risk. susceptibility. OP can be divided into two categories: primary OP and secondary OP. The former can occur in all genders and age groups, but it is more common in postmenopausal women and middle-aged and elderly men over 50 years old; the latter is mainly due to the use of drugs (such as glucocorticoids, immunosuppressants) and various diseases (such as Cushing syndrome, hyperparathyroidism, kidney disease, diabetes mellitus, multiple myeloma, vitamin D deficiency, and hypogonadism). Osteoporotic fractures (Osteoporotic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/711A61K47/69A61K47/60A61P19/10A61P1/02B82Y5/00B82Y40/00
CPCA61K31/711A61K47/6935A61K47/60A61P19/10A61P1/02B82Y5/00B82Y40/00
Inventor 周永胜牛宇霆杨洋杨振刘燕王叙
Owner PEKING UNIV SCHOOL OF STOMATOLOGY
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