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Hyaluronic acid-methotrexate self-assembled nanomicelle and preparation method thereof

A technology of methotrexate and hyaluronic acid, used in drug combinations, pharmaceutical formulations, and inactive medical preparations, etc., can solve the problems of chemotherapy failure, easy breakage of disulfide bonds, life-threatening problems, etc. release, improve bioavailability, and reduce toxic and side effects

Inactive Publication Date: 2018-11-27
NORTHWEST UNIV(CN)
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Problems solved by technology

[0003] Chemotherapy is the most important means of treating cancer besides surgery. There are two main problems: one is the high toxicity of drugs, which reduces the number of white blood cells, red blood cells and platelets in cancer patients receiving chemotherapy, and causes nausea, vomiting and hair loss in patients. side effects, even life-threatening
The second is the drug resistance of tumors (cancer cells). Although most cancer patients respond to drugs at the initial stage of chemotherapy, the drug resistance mechanism of tumors often leads to the failure of chemotherapy and the death of patients.
In addition, the concentration of glutathione (GSH) in tumor cells is much higher than that in normal tissue environment, so disulfide bonds are easily broken
[0006] Methotrexate (MTX) is an effective anti-tumor drug, but now it is mostly tablets and injections in clinical practice, and the drug released after use has no target certainty, and it is absorbed and metabolized by various parts of the human body

Method used

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  • Hyaluronic acid-methotrexate self-assembled nanomicelle and preparation method thereof
  • Hyaluronic acid-methotrexate self-assembled nanomicelle and preparation method thereof
  • Hyaluronic acid-methotrexate self-assembled nanomicelle and preparation method thereof

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Embodiment Construction

[0035] The present invention will be further described in detail below in conjunction with specific embodiments, which are explanations of the present invention rather than limitations.

[0036] The English letters that appear in the present invention are expressed as follows:

[0037] HA-SS-MTX means: hyaluronic acid-disulfide bond-methotrexate;

[0038] DA means: cystamine; HA means: hyaluronic acid;

[0039] DA-MTX means: cystamine-methotrexate;

[0040] EDC is: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride;

[0041] NHS is: N-hydroxysuccinimide.

[0042] 1. Preparation of HA-SS-MTX polymer micelles

[0043]The invention utilizes the targeting property of hyaluronic acid, uses disulfide bond-containing cystamine as a bridge, connects drug MTX with anti-tumor effect, and prepares HA-SS-MTX polymer micelles through dialysis.

[0044] 1. Preparation of HA-SS-MTX polymer system

[0045] MTX contains -COOH, cystamine contains -NH 2 , by controlling the ratio...

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Abstract

The invention belongs to the technical field of nano pharmaceutical preparations and discloses a hyaluronic acid-methotrexate self-assembled nanomicelle and a preparation method thereof. Hyaluronic acid and methotrexate are connected through disulfide-bond cystamine to prepare the hyaluronic acid-methotrexate self-assembled nanomicelle through dialysis. By adoption of the disulfide-bond cystamineas a linkage factor, MTX and hyaluronic acid are connected to form the self-assembled nanomicelle, on the one hand, hyaluronic acid which can be specifically combined with tumor cells enables a targeting effect of the polymeric micelle, and medicines can be targetedly loaded to a lesion; on the other hand, by glutathione responsiveness of disulfide bond, controlled release of the medicines can berealized.

Description

technical field [0001] The invention belongs to the technical field of nano-pharmaceutical preparations, and in particular relates to a hyaluronic acid-methotrexate self-assembled nano-micelle and a preparation method thereof. Background technique [0002] Tumors are abnormal cell groups that do not grow according to the metabolic laws of normal human cells, and are not restrained and controlled. Clinically, scientists have been fighting against tumors, but the cure rate of tumors has not yet shown a significant upward trend. Chen Wanqing led his team to collate and analyze the data of the National Cancer Registry Center. The report shows that in 2015, the number of malignant tumors in China was 4.292 million and the number of deaths was 2.814 million. In cities, there are 191.5 cases per 100,000 people, and 109.5 deaths per 100,000 people; in rural areas, these two data are significantly higher than those in cities, with 213.6 cases per 100,000 people, and 109.5 deaths per...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K9/107A61K31/519A61P35/00
CPCA61K9/1075A61K31/519A61K47/61A61P35/00
Inventor 黄赛朋成杰伟薛伟明李文帅温惠云
Owner NORTHWEST UNIV(CN)
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