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Multifunctional bionic HA particles loaded curcumin prodrug micro-nano composite material, preparation method and application thereof

A multifunctional, composite material technology, applied in chemical instruments and methods, pharmaceutical science, phosphorus compounds, etc., can solve the problem of drug loading rate of only about 2-3%, and achieve enhanced anti-cancer effect, growth inhibition, excellent Bone-promoting effect

Active Publication Date: 2020-12-11
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Literature (Lee, W.-H., C.-Y.Loo, and R. Rohanizadeh, Functionalizing the surface of hydroxyapatite drug carrier with carboxylic acid groups to modulate the loading and release of curcumin nanoparticles. Materials Science & Engineering C-Materials for Biological Applications, 2019.9 : p.929-939.) Although the chemical modification of the surface of HA particles has improved the loading capacity of curcumin nano-medicines to a certain extent and achieved a certain tumor-suppressing effect, but its drug loading rate is only about 2-3%.

Method used

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  • Multifunctional bionic HA particles loaded curcumin prodrug micro-nano composite material, preparation method and application thereof
  • Multifunctional bionic HA particles loaded curcumin prodrug micro-nano composite material, preparation method and application thereof
  • Multifunctional bionic HA particles loaded curcumin prodrug micro-nano composite material, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The preparation of curcumin nanometer prodrug comprises the steps:

[0045] (1) mPEG-modified SA with a molecular weight of 550: Weigh 8 g of mPEG 550 , 1.6 g of succinic anhydride, and 0.56 g of p-toluenesulfonic acid were placed in a flask, under nitrogen environment protection, and reacted at 80° C. for 3 h. The finished product was dissolved in 30ml of dichloromethane, filtered to get the filtrate, and then recrystallized repeatedly with 160mL of anhydrous ether at -5°C, freeze-dried to obtain the mPEG product modified with SA (mPEG 550 -SA);

[0046] (2) mPEG 550 -SA modified curcumin: take the mPEG product (mPEG) modified with SA described in step (1). 350 -SA) 2.7g, curcumin (0.54g), N,N'-dicyclohexylcarbodiimide (1.4g), 4-dimethylaminopyridine (0.1g), triethylamine (0.1mL) In an ultra-dry dichloromethane solution (50ml), under a nitrogen protection environment for 12h, filter the reacted solution to remove the precipitate, then mix the filtrate with 250mL an...

Embodiment 2

[0048] The preparation of composite micro-nano particles comprises the following steps:

[0049] (1) Preparation of hydroxyapatite powder with hierarchical structure: 4 mM diammonium hydrogen phosphate was prepared, and the pH was adjusted to 6 to obtain solution a. Add calcium nitrate to solution a, the molar volume ratio of calcium nitrate to solution a is 6.6:1 mmol / L, stir well to obtain solution b. Then 1 mmol sodium citrate was added to solution b and stirred vigorously, and the mixture was transferred to a polytetrafluoroethylene-lined autoclave, and reacted at 180 °C for 3 h. The resulting precipitate was centrifuged and freeze-dried to prepare HA particles. The HA particles have a relatively high hollow structure with a specific surface area of ​​up to 64.8m 2 / g.

[0050] (2) Preparation of HA particle-loaded curcumin prodrug composite micro-nanoparticles: Weigh 20mg HA particles and 20mg grafted with mPEG prepared in Example 1 550 -The curcumin prodrug of SA was...

Embodiment 3

[0052] The preparation of composite micro-nano particles comprises the following steps:

[0053] (1) Preparation of biomimetic HA micro-nanoparticles: 6.0 mM diammonium hydrogen phosphate was prepared, and the pH was adjusted to 6 to obtain solution a. Add calcium nitrate to solution a, the molar volume ratio of calcium nitrate to solution a is 10:1mmol / L, stir well to obtain solution b. Then 1.5 mmol of sodium citrate was added to solution b and stirred vigorously, and the mixture was transferred to a polytetrafluoroethylene-lined autoclave, and reacted at 180 °C for 3 h. The resulting precipitate was centrifuged and freeze-dried to prepare HA particles. The HA particles have a relatively high hollow structure with a specific surface area of ​​up to 74.8m 2 / g.

[0054] (2) Preparation of HA particle-loaded curcumin prodrug composite micro-nanoparticles: Weigh 20mg HA particles and 20mg grafted with mPEG prepared in Example 1 550 -The curcumin prodrug of SA was dissolved ...

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Abstract

The invention discloses a multifunctional bionic HA particles loaded curcumin prodrug micro-nano composite material, a preparation method and an application thereof. The method comprises the followingsteps, preparing hydroxyapatite micro-nano particles with a bionic structure; preparing a curcumin nano prodrug; adding hydroxyapatite powder and the curcumin nano prodrug into water, uniformly mixing the mixture, and carrying out incubating, adsorbing, centrifuging, freeze-drying and sterilizing to obtain the composite micro-nano particles. The prepared composite micro-nano particles of the present invention have high drug loading capacity, a selective targeting function, good biocompatibility and no obvious toxic or side effect on living organisms. In high drug loading capacity, the composite particles can effectively inhibit growth of bone tumors. In minor drug loading capacity, the micro-nano multistage structure of the composite particles can efficiently promote regeneration and repair of bone tissues.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a multifunctional bionic HA particle-loaded curcumin prodrug micro-nano composite material and a preparation method and application thereof. Background technique [0002] Osteosarcoma, the most common primary bone tumor in children and adolescents, readily metastasizes to the lungs. Complete radical resection is currently the first choice for the clinical treatment of osteosarcoma. However, the vast majority of cases are difficult to be completely resected during surgery. Therefore, postoperative chemotherapy is essential to kill residual cancer cells. Although high-dose traditional drug therapy has achieved good clinical effects, chemotherapy can easily cause serious sequelae. In addition, in order to alleviate the limitation of the patient's limb movement, the bone tissue defect caused by the operation also needs to be repaired or reconstructed. The...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/12A61L27/18A61L27/54A61L27/58C01B25/32C08G65/331C08G65/334
CPCA61L27/12A61L27/18A61L27/54A61L27/58A61L2300/216A61L2300/404A61L2300/416A61L2430/02C01B25/325C01B25/327C01P2004/03C01P2004/32C01P2004/62C08G65/331C08G65/3346C08L71/02
Inventor 王迎军杜昶徐东万宇欣
Owner SOUTH CHINA UNIV OF TECH
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