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Nano drug and preparation method thereof

A nano drug and drug technology, applied in the direction of pharmaceutical formula, drug combination, antineoplastic drugs, etc., can solve the problems of low drug solubility, reduced efficiency, drug resistance, healthy organ toxicity, etc., to achieve high drug loading and enhanced bioavailability Degree and stability, highly dispersive effect

Inactive Publication Date: 2019-07-12
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, its efficacy is limited by low drug solubility, non-selectivity, toxicity to healthy organs, reduced efficiency, and drug resistance

Method used

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  • Nano drug and preparation method thereof
  • Nano drug and preparation method thereof
  • Nano drug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1: the synthesis of compound 1

[0055] First dissolve 50mg of paclitaxel in 3ml of DMF, then add 13.95mg of 4,4'-dithiodibutyric acid to it, and then add 24.69mg of EDCI (1-(3- Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) and 0.7mg DMAP (4-dimethylaminopyridine), after stirring at room temperature for 1 hour, continue to add 12.35mg EDCI and 0.7mg DMAP, and stir at room temperature for two days , and observe the progress of the reaction at a sampling point every 1 hour, and stop the reaction after all the raw materials have reacted.

[0056] After the reaction, the reactant was first dissolved in dichloromethane, and then extracted with water two to three times, and the aqueous phase was collected to continue the extraction on both sides. All the obtained organic phases were collected, spin-dried and then sanded, and the ratio of methanol: dichloromethane 1:40 was passed through a silica gel column, and the product was purified to obtain compound...

Embodiment 2

[0058] Embodiment 2: the synthesis of compound 2

[0059] Dissolve 20mg of compound 1 in 3ml of DMF, then add 9.8mg of gemcitabine to it, and then add 7.85mg of EDCI and 0.25mg of DMAP to it after it is completely dissolved, stir at room temperature for 1 hour, then continue to add 3.93mg of gemcitabine EDCI and 0.25 mg of DMAP were stirred at room temperature for two days, and the reaction progress was observed by sampling half an hour every other hour, and the reaction could be stopped when all the raw materials were reacted.

[0060] After the reaction, the reactant was first dissolved in dichloromethane, and then extracted with water two to three times, and the aqueous phase was collected to continue the extraction on both sides. All the obtained organic phases were collected, spin-dried and then sanded, and the ratio of methanol:dichloromethane 1:20 was passed through a silica gel column, and the product was purified to obtain compound 2, and the H NMR spectrum image 3 ...

Embodiment 3

[0062] Example 3: Self-assembly of nanoparticles without stabilizers

[0063] Dissolve 5mg of compound 2 in 1ml of acetone, suck it up with a syringe, and slowly place it in 38ml of pure water placed in an ultrasonic device, and control the dropping rate at 5μL / s. After the addition of the organic phase is completed, Continue to sonicate for 1 h, and a clear milky white colloid is obtained at this time. The colloid is freeze-dried to obtain drug nanoparticles. The nanoparticles were observed by transmission electron microscopy as Figure 8 As shown, the particle size is uniform, and the particle size of most nanoparticles is between 150nm and 200nm.

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Abstract

The invention discloses a nano drug and a preparation method thereof, in particular to a nano drug simultaneously carrying a hydrophobic drug body and a hydrophilic drug body. The hydrophobic drug body A and the hydrophilic drug body B are connected with each other through a disulfide bond which can be cut by GSH and then self-assembled into a nanoparticle, namely the nano drug. A prodrug with onehydrophilic end and one hydrophobic end is formed and can be self-assembled into nano liposome in water, the drug can be effectively delivered, and the synergistic application of the hydrophobic drugbody (such as paclitaxel) and the hydrophilic drug body (such as gemcitabine) can be achieved at the same time. The drug is prepared through an esterification reaction and has the following advantages of low cost, easy preparation, high drug loading capacity and the like.

Description

technical field [0001] The invention belongs to the technical field of nanomedicine, and relates to a nanomedicine and a preparation method thereof. Background technique [0002] Cancer is one of the most devastating diseases in the world and a leading cause of death. More than 10 million new cases will be diagnosed each year, and cancer-related deaths are expected to reach 12 million in 2030. Therefore, cancer treatment is a great challenge in the twenty-first century. Chemotherapy with anticancer drugs is an important method of cancer treatment. [0003] However, its efficacy is limited by low drug solubility, non-selectivity, toxicity to healthy organs, reduced efficiency, and drug resistance. Polymeric micellar nanoparticles are one of the most important drug carriers in cancer nanomedicine. [0004] Most of these micellar structures consist of a hydrophobic core for drug loading and a pegylated hydrophilic shell for improved colloidal stability and stealth effect. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K31/7068A61K47/55A61P35/00A61K31/337
CPCA61K9/19A61K31/337A61K31/7068A61K47/55A61P35/00
Inventor 陈海燕万浩李瑞熙
Owner CHINA PHARM UNIV
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