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A preparation method of nanometer drug-loaded micelles loaded with daptomycin and small-molecule hydrophobic drugs

A hydrophobic drug, daptomycin technology, applied in the field of biomedical nanomaterials, can solve the problems of difficult large-scale preparation and accurate preparation of carriers, complex synthesis process, complex structure, etc., and achieve excellent resistance to non-specific protein adsorption Performance, simple preparation conditions, and mild reaction conditions

Active Publication Date: 2021-08-27
YANSHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these nano-drug carriers have the disadvantages of complex structure and complex synthesis process, which makes it difficult to prepare these carriers on a large scale and accurately, and there are certain differences between batches of products. Production of macromolecules helps to avoid these problems
[0004] In addition, the existing nano-drug carriers will adsorb protein molecules in the living body, causing the nano-drugs to be easily removed by the reticuloendothelial system, and often bring a certain degree of toxicity in the living body

Method used

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  • A preparation method of nanometer drug-loaded micelles loaded with daptomycin and small-molecule hydrophobic drugs
  • A preparation method of nanometer drug-loaded micelles loaded with daptomycin and small-molecule hydrophobic drugs
  • A preparation method of nanometer drug-loaded micelles loaded with daptomycin and small-molecule hydrophobic drugs

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Embodiment 1

[0041] Doxorubicin is selected as the small molecule hydrophobic drug of this embodiment, and the method for preparing nano-drug-loaded micelles includes the following steps:

[0042] S1, prepare doxorubicin hydrochloride methanol solution;

[0043] Dissolve 1.5 mg of doxorubicin hydrochloride in 1 mL of methanol to prepare 1.5 mg / mL of doxorubicin hydrochloride methanol solution;

[0044] Preparation of doxorubicin methanol solution;

[0045] Take 400 μL of doxorubicin hydrochloride methanol solution, then add 16.2 μL of triethylamine, and sonicate for 1 h in the dark to obtain doxorubicin methanol solution;

[0046] S2, prepare daptomycin methanol solution;

[0047] According to the mass ratio of methanol to daptomycin 1:0.0076, prepare 6 mg / mL daptomycin methanol solution;

[0048] S3, preparing nano-drug loaded micelles;

[0049] Take 300 μL of doxorubicin methanol solution and 750 μL of daptomycin methanol solution in a 5 mL round-bottomed flask, and at room temperatu...

Embodiment 2

[0060] S1, prepare doxorubicin hydrochloride methanol solution;

[0061] Dissolve 1 mg doxorubicin hydrochloride in 1 mL methanol to prepare 1 mg / mL doxorubicin hydrochloride methanol solution;

[0062] Preparation of doxorubicin methanol solution;

[0063] Take 400 μL of doxorubicin hydrochloride methanol solution, then add 0.3 μL of triethylamine, and sonicate in the dark for 1 h to obtain doxorubicin methanol solution;

[0064] S2, prepare daptomycin methanol solution;

[0065] According to the mass ratio of methanol to daptomycin 1:0.001, prepare 1 mg / mL daptomycin methanol solution;

[0066] S3, preparing nano-drug loaded micelles;

[0067] Take 300 μL of doxorubicin methanol solution and 300 μL of daptomycin methanol solution in a 5 mL round-bottomed flask, at room temperature, in a water bath at a speed of 3000 rpm for 6 h in the dark and in a temperature bath, and then the mixed methanol solution was added to the flask. It was added dropwise to 12 mL of water at a ...

Embodiment 3

[0069] S1, prepare doxorubicin hydrochloride methanol solution;

[0070] Dissolve 10 mg of doxorubicin hydrochloride in 1 mL of methanol to prepare a 10 mg / mL doxorubicin methanol solution;

[0071] Preparation of doxorubicin methanol solution;

[0072] Take 200 μL of doxorubicin hydrochloride methanol solution, then add 32.4 μL of triethylamine, and sonicate for 1 h in the dark to obtain doxorubicin methanol solution;

[0073] S2, prepare daptomycin methanol solution;

[0074] According to the mass ratio of methanol to daptomycin 1:0.0126, prepare 10 mg / mL daptomycin methanol solution;

[0075] S3, preparing nano-drug loaded micelles;

[0076] Take 100 μL of doxorubicin methanol solution and 10 mL of daptomycin methanol solution in a 25 mL round-bottomed flask, at room temperature, heat in a water bath at a speed of 100 rpm for 6 h in the dark and in a warm bath, and then the mixed methanol solution is gradually added. It was added dropwise to 8 mL of water at a rate of 0...

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Abstract

The present invention relates to a preparation method of nanometer drug-loaded micelles loaded with daptomycin and small-molecule hydrophobic drugs, which comprises the following steps: S1, preparing a 0.1-10 mg / mL methanol solution of small-molecule hydrophobic drugs; S2 1. Prepare a methanol solution of daptomycin at 1-10 mg / mL; S3. Prepare nano drug-loaded micelles; Methanol solution and methanol solution of small molecule hydrophobic drugs are evenly mixed. After warm bathing in the dark, the mixed methanol solution is added to water drop by drop. Stability and Dispersion of Daptomycin Micelles Encapsulating Small Molecule Hydrophobic Drugs in Nano-Drug-loaded Micelles. The nanometer drug-loaded micelles of the present invention exhibit tumor targeting ability through enhanced penetration and retention effects, release small-molecule anticancer drugs faster at weakly acidic parts of tumors, and have good antibacterial properties and excellent antitumor effects.

Description

technical field [0001] The invention belongs to the technical field of biomedical nanomaterials, and in particular relates to a preparation method of nanometer drug-loaded micelles containing small-molecule hydrophobic drugs with daptomycin. Background technique [0002] It is reported that cancer is increasingly becoming the number one killer of people's health and development. Currently, chemotherapy is still the main method of treating cancer. However, commonly used small-molecule drugs in chemotherapy, such as doxorubicin, paclitaxel, and camptothecin, have defects such as low solubility, large toxic and side effects, low tumor targeting, and easy development of drug resistance. [0003] In order to overcome the shortcomings of the above-mentioned small molecule drugs, researchers have developed many nano-drug carriers to improve the effect of small molecule drugs in the treatment of tumors and reduce the toxic and side effects of small molecule drugs on normal tissues....

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/10A61K45/06A61K41/00A61K9/107A61P35/00A61K31/704A61K31/337A61K31/4745
CPCA61K9/1075A61K31/337A61K31/4745A61K31/704A61K38/10A61K41/0071A61K45/06A61P35/00A61K2300/00
Inventor 王龙刚郭全领
Owner YANSHAN UNIV