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A kind of pH-sensitive nano-medicine based on calcium carbonate coordination chelation drug and its preparation method and application

A nano-drug, calcium carbonate technology, applied in the field of biomedical applications, can solve the problems of inability to pass the tumor EPR effect, inability to endocytosis, poor water solubility, etc., and achieve the effects of high drug loading rate, improved stability, and stable drug loading.

Active Publication Date: 2021-06-08
NORTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the research, an organic matrix is ​​usually used to regulate the reaction of calcium chloride and anhydrous sodium carbonate to form micron-sized mesoporous hollow spheres, which are used to load anti-tumor drugs and obtain micron-sized pH-sensitive drug carriers (Journal of Colloid & Interface Science, 2017, 502 ,59.), however, there are certain problems in the subsequent biomedical application of micron-sized pH-sensitive calcium carbonate, such as the inability to pass through the EPR effect of tumors, inability to endocytosis, etc.
And its exterior has not been modified by polymers, so it has poor water solubility and is easy to decompose in the body circulation

Method used

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  • A kind of pH-sensitive nano-medicine based on calcium carbonate coordination chelation drug and its preparation method and application
  • A kind of pH-sensitive nano-medicine based on calcium carbonate coordination chelation drug and its preparation method and application
  • A kind of pH-sensitive nano-medicine based on calcium carbonate coordination chelation drug and its preparation method and application

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preparation example Construction

[0033] The preparation process of the present invention is as follows:

[0034] 1) According to the ratio of absolute ethanol: ethanol solution of additives: calcium chloride = 80mL: (200-800) L: (50-150) mg, dissolve calcium chloride in absolute ethanol, and then add the additive solution , and stir evenly to obtain solution A; wherein, the concentration of the ethanol solution of the additive is 0.4mol / L; wherein, the additive is polyacrylic acid, phytic acid or polypeptide.

[0035]2) According to the dosage ratio of absolute ethanol:antineoplastic drug=20mL:(3~10) mg, add antineoplastic drug into absolute ethanol, stir evenly, obtain the ethanol solution of antineoplastic drug; Add the ethanol solution dropwise to the solution A obtained in step 1), and let it stand for 2 to 4 hours after the dropping to obtain a mixed solution B; wherein, the mass ratio of calcium chloride to the antineoplastic drug is (50 to 150): (3 to 10); the antitumor drug is curcumin, doxorubicin, ...

Embodiment 1

[0041] A preparation method of pH-sensitive nano-medicine based on calcium carbonate coordination chelation drug is as follows:

[0042] 1) Put 5g of ammonium bicarbonate into two clean dry small beakers (2 small beakers, each 2.5g);

[0043] 2) Take two beakers (250mL and 100mL), add 80mL of absolute ethanol to one of the 250mL beakers, and then add 150mg of CaCl 2 Stir and dissolve with 500L PAA (polyacrylic acid), add 20mL absolute ethanol to another 100mL beaker, then add 5mg curcumin (CCM), stir and dissolve, wait until the material in each beaker is completely dissolved, put the solution in the small beaker Add it dropwise into a large beaker, let it stand for chelation for 2 to 4 hours to obtain a mixed solution, and then place it in a vacuum oven (30°C) for 48 hours to react to obtain amorphous calcium carbonate-curcumin;

[0044] 3) Centrifuge and wash the obtained amorphous calcium carbonate-curcumin with ethanol and water for 6 times, 10min at 8000rpm, and freeze-d...

Embodiment 2

[0050] 1) According to the ratio of absolute ethanol: ethanol solution of additives: calcium chloride = 80mL: 200L: 50mg, dissolve calcium chloride in absolute ethanol, then add the additive solution, stir evenly, and obtain solution A; wherein, The concentration of the ethanol solution of the additive is 0.4mol / L; wherein, the additive is polyacrylic acid.

[0051] 2) According to the dosage ratio of absolute ethanol:antineoplastic drug=20mL:3mg, add the antineoplastic drug into the absolute ethanol, stir evenly to obtain the ethanol solution of the antineoplastic drug; add the ethanol solution of the antineoplastic drug dropwise to In the solution A obtained in step 1), let it stand for 2 hours after dripping to obtain a mixed solution B; wherein, the mass ratio of calcium chloride to the antineoplastic drug is 150:3; the antineoplastic drug is curcumin.

[0052] 3) According to the dosage ratio of ammonium bicarbonate: antineoplastic drug = 5 mg: 3 mg, the mixed solution B ...

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Abstract

A kind of pH-sensitive nano-medicine based on calcium carbonate coordination chelation drug and its preparation method and application, calcium chloride is dissolved in absolute ethanol, then add additive solution, stir evenly, obtain solution A; Ethanol of antineoplastic drug The solution was added dropwise to solution A, and left to stand after dropping to obtain a mixed solution B; the mixed solution B and ammonium bicarbonate were placed in a vacuum oven for reaction, then dissolved in dichloromethane, and then added carboxyl-containing high Molecular substances, after stirring evenly, add 4-dimethylaminopyridine and dicyclohexylcarbodiimide, rise to room temperature, and continue to react in the dark to obtain pH-sensitive nano-medicines based on calcium carbonate coordination and chelation drugs. The preparation method of the present invention has mild conditions, easy operation, controllable size of nano medicine and good stability. The drug carrier prepared by the invention can selectively release anti-tumor drugs according to the difference in pH environment of tumor tissues and can be applied in the preparation of anti-tumor drugs.

Description

technical field [0001] The invention belongs to the technical field of biomedical applications, and relates to a preparation method and application of a pH-sensitive nano-medicine based on calcium carbonate coordination and chelation drugs. Background technique [0002] Malignant tumors are major diseases that seriously endanger human life and health, and the morbidity and mortality are increasing year by year. Surgical treatment and chemotherapy are the main means of current clinical treatment, but there are problems such as large trauma and large side effects, especially chemotherapy based on the general dose of the group, which has large side effects. In recent years, nano drug delivery systems have brought new opportunities for the treatment of tumors, which can be used to improve drug targeting and reduce drug side effects. [0003] In recent years, researchers have used pH-sensitive drug carriers to load anti-tumor drugs for the treatment of tumors. People use the di...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/19A61K47/61A61K47/60A61K47/54A61K47/52A61P35/00A61K31/12A61K31/704A61K31/352A61K31/05
CPCA61K9/19A61K31/05A61K31/12A61K31/352A61K31/704A61K47/52A61K47/545A61K47/60A61K47/61A61P35/00
Inventor 温惠云彭佳佳宋春丽薛伟明黄赛朋贺艺舒
Owner NORTHWEST UNIV
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