Method for improving dispersibility of insoluble amorphous calcium phosphate

An amorphous calcium phosphate, dispersion technology, applied in the direction of inorganic non-active ingredients, pharmaceutical formulations, active ingredients of ketones, etc., can solve problems such as agglomeration and precipitation, difficult to make pharmaceutical preparations, large specific surface area, etc., to improve Utilization rate, excellent inhibition ability, effect of large specific surface area

Inactive Publication Date: 2020-01-14
TAIYUAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the large specific surface area of ​​ACP particles, they are prone to agglomeration and precipitation in aqueous solution, making it difficult to make intravenously injectable pharmaceutical preparations

Method used

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  • Method for improving dispersibility of insoluble amorphous calcium phosphate
  • Method for improving dispersibility of insoluble amorphous calcium phosphate
  • Method for improving dispersibility of insoluble amorphous calcium phosphate

Examples

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Effect test

Embodiment 1

[0026] This example provides a preparation method for improving the dispersibility of insoluble amorphous calcium phosphate, which includes the following steps: firstly prepare ACP nanoparticles by co-precipitation method, then add them into an aqueous solution of sodium hexametaphosphate, and disperse them ultrasonically to form a stable suspension. Specific steps are as follows:

[0027] Prepare 29 mL of calcium nitrate aqueous solution, Ca 2+ The concentration is 0.034 mol / L; prepare 29 mL diammonium hydrogen phosphate aqueous solution, PO 4 3- The concentration is 0.024 mol / L. According to the molar ratio Ca / P=1.5, the diammonium hydrogen phosphate solution was added dropwise to the calcium nitrate solution under the condition of 30 ºC, and the NaOH solution was adjusted to pH 8. After stirring for 10 min, let it stand for 12 h, and centrifuge. Washing and drying to obtain ACP nanoparticles. Mix the above-mentioned ACP nanoparticles with sodium hexametaphosphate (mass ...

Embodiment 2

[0030] Prepare 29 mL of calcium nitrate aqueous solution, Ca 2+ The concentration is 0.034 mol / L; prepare 25 mL diammonium hydrogen phosphate aqueous solution, PO 4 3- The concentration is 0.028 mol / L. According to the molar ratio Ca / P = 1.5, the diammonium hydrogen phosphate solution was added dropwise to the calcium nitrate solution at 25 ºC, and the NaOH solution was adjusted to pH 7. After stirring for 1 h, let it stand for 12 h, and centrifuge. Washing and drying to obtain ACP nanoparticles. The average particle size measured by the laser particle size analyzer is 126 nm (such as figure 2 shown). Mix the above-mentioned ACP nanoparticles with sodium hexametaphosphate (mass ratio is 1:5), add them into water, disperse uniformly with the probe ultrasonic, the ultrasonic power of the probe is 500 W, ultrasonic 3 s, intermittent 2 s, to obtain a stable suspension of nanocomposite particles liquid and dried to obtain nanocomposite particles.

Embodiment 3

[0032] Prepare 29 mL of calcium nitrate aqueous solution, Ca 2+ The concentration is 0.034 mol / L; prepare 20 mL diammonium hydrogen phosphate aqueous solution, PO 4 3- The concentration is 0.034 mol / L. According to the molar ratio Ca / P = 1.5, the diammonium hydrogen phosphate solution was added dropwise to the calcium nitrate solution at 40 ºC, and the NaOH solution was adjusted to pH 9. After stirring for 2 hours, let it stand for 12 hours, and centrifuge. Washing and drying to obtain ACP nanoparticles. From the SEM images ( image 3 ), it can be seen that the formed nanocomposite particles are spherical, with a particle size of about 100 nm and uniform particle size. Mix the above-mentioned ACP nanoparticles with sodium hexametaphosphate (mass ratio is 1:3), add them into water, disperse uniformly with the probe ultrasonic, the ultrasonic power of the probe is 300 W, ultrasonic 3 s, intermittent 2 s, to obtain a stable suspension of nanocomposite particles liquid and dr...

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Abstract

The invention discloses a method for improving the dispersibility of insoluble amorphous calcium phosphate, provides a method for dispersing and encapsulating a drug by using the insoluble amorphous calcium phosphate, and belongs to the technical field of biomaterials. According to the method, firstly, amorphous calcium phosphate nanoparticles are prepared by adopting a co-precipitation method, then are added to an aqueous solution of sodium hexametaphosphate, and are subjected to probe ultrasonic treatment to form spherical particles. The preparation method is simple and fast, no surfactant is added, the prepared nanoparticles have a uniform particle size and good dispersion stability and can be stably dispersed at room temperature for one month, the nanoparticles have good pH response and release properties to the drug, the amount of release of the drug under simulated tumor pH environment is higher than the amount of release under normal tissue environment, at the same time, the dugload nanoparticles loaded with curcumin (Cur) show excellent inhibitory ability on A549 cells, the survival rate of cancer cells is significantly decreased, and using as an ideal carrier for chemotherapy drugs can be realized.

Description

technical field [0001] The invention relates to a method for improving the dispersibility of insoluble amorphous calcium phosphate, belonging to the technical field of biomaterials. Background technique [0002] The third national cause of death survey data show that cancer has become the second leading cause of death in my country. According to statistics, more than 3 million patients suffer from such problems every year in our country and need timely treatment. Therefore, solving this problem has important social significance. At present, the means of tumor treatment mainly include surgery, radiotherapy, chemotherapy or biological therapy, etc., and chemotherapy is an effective therapy before and after tumor surgery. However, small-molecule anti-tumor drugs have short half-lives in vivo, large doses, and poor selectivity, which can cause severe toxic and side effects on normal tissues and organs, and most anti-tumor drugs have drug resistance problems. Long-term use can ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/52A61K47/02A61K31/12A61P35/00
CPCA61K9/5115A61K31/12A61P35/00
Inventor 牛宝龙李文凤饶超辉连小洁贾兰
Owner TAIYUAN UNIV OF TECH
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