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Preparation method of anti-tumor nanoparticle drug

A nanoparticle, anti-tumor technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as unseen, difficult to exert tumor treatment effects, destroy tumor cell microenvironment, etc., achieve controllable particle size, The effect of avoiding encapsulation efficiency problems and simplifying the preparation process

Active Publication Date: 2017-03-15
蒋鸥
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, although bisphosphonates have been found to have obvious anti-tumor effects in vitro experiments, within 24 hours after intravenous infusion in vivo, they quickly accumulate in bones, and the rest (44±18%) are excreted into urine through the kidneys. , so it is difficult to play a therapeutic effect on solid tumors
[0010] The conception and design of the nanoparticle drugs developed in this project are chemically modified, and groups that can target M2 macrophages and have apoptosis effects, such as mannose, imidazole and etidronate, are introduced into the nanoparticles. The core-shell and core of the drug not only destroy the microenvironment that tumor cells rely on for survival, but also make the drug with apoptosis effect form a high concentration in the local tumor without additional loading of drugs, so as to achieve therapeutic effect. Other literature search and novelty search, no similar reports

Method used

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  • Preparation method of anti-tumor nanoparticle drug
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  • Preparation method of anti-tumor nanoparticle drug

Examples

Experimental program
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Embodiment 1

[0042] 1. Synthesis of carboxymethyl chitosan modified by imidazole and mannose

[0043] Step 1: Prepare morpholineethanesulfonic acid (MES) buffer solution: take 6g of MES, 300ml of distilled water, configure the concentration as 5mg / ml, adjust the pH value to 4 with NaOH,

[0044] Step 2: Take 100 mg of carboxymethyl chitosan (O-CMC) and add it to 100 ml of MES buffer solution configured in step 1, stir until it is clear and transparent, and obtain a O-CMC solution with a concentration of 1 mg / ml.

[0045] Step 3: Add α-D-mannopyranose-4-aminophenyl glycoside (MAN) into the MES buffer prepared in step 1, stir until clear and transparent, and obtain a MAN solution with a concentration of 1 mg / ml,

[0046] Step 4: Mix 100ml of the solution prepared in step 2 with 10ml of the solution prepared in step 3 and add 70.4mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N -Hydroxysuccinimide (NHS) 7 mg was mixed and stirred at a temperature of 15°C, and sti...

Embodiment 2

[0056] 1. Synthesis of carboxymethyl chitosan modified by imidazole and mannose

[0057] Step 1: Prepare morpholineethanesulfonic acid (MES) buffer solution: Dissolve MES in distilled water to a concentration of 50 mg / ml, adjust the pH value to 7 with NaOH,

[0058] Step 2: Add carboxymethyl chitosan (O-CMC) to the MES buffer solution prepared in step 1, stir until clear and transparent, and prepare a O-CMC solution with a concentration of 10 mg / ml.

[0059] Step 3: Add α-D-mannopyranose-4-aminophenyl glycoside (MAN) into the MES buffer prepared in step 1, stir until clear and transparent, and prepare a MAN solution with a concentration of 10 mg / ml.

[0060] Step 4: Mix 100ml of the solution prepared in step 2 with 100ml of the solution prepared in step 3 and add 704mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N- Hydroxysuccinimide (NHS) 70 mg was mixed and stirred at a temperature of 95°C, and stirred until the liquid evaporated completely to o...

Embodiment 3

[0070] 1. Synthesis of carboxymethyl chitosan modified by imidazole and mannose

[0071] Step 1: Prepare morpholineethanesulfonic acid (MES) buffer solution: take MES and configure it with distilled water to a concentration of 25 mg / ml, adjust the pH value to 6 with NaOH,

[0072] Step 2: Add carboxymethyl chitosan (O-CMC) to the MES buffer solution configured in step 1, stir until clear and transparent, and obtain a concentration of 5 mg / ml O-CMC solution,

[0073] Step 3: Add α-D-mannopyranose-4-aminophenyl glycoside (MAN) into the MES buffer prepared in step 1, stir until clear and transparent, and obtain a MAN solution with a concentration of 5 mg / ml,

[0074] Step 4: Mix 100ml of the solution prepared in step 2 with 50ml of the solution prepared in step 3 and add 704mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N- Hydroxysuccinimide (NHS) 70 mg was mixed and stirred at a temperature of 15°C, and stirred until the liquid evaporated completely...

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Abstract

The invention provides a preparation method of an anti-tumor nanoparticle drug. According to the method, etidronic acid is taken as a core, etidronic acid and carboxymethyl chitosan modified with two groups of imidazole and mannose are prepared into the nanoparticle drug by means of ionic gelation, treatment effect on resistance to malignant tumor is realized by targeting to a lot of M2 macrophages present at the tumor lesion part and enabling the macrophages to apoptosis so as to intervene the microenvironment for existence of tumor, targeting performance of nano in malignant tumor treatment is realized, drug entrapment efficiency of nanoparticles is avoided, and steps of anti-tumor nanoparticle drug preparation are simplified. Since anti-tumor effect of the drug is achieved without chemotherapeutic drugs, the anti-tumor nanoparticle drug cannot cause toxic and side effects similar to chemotherapeutic drugs while treating malignant tumor.

Description

technical field [0001] The invention relates to the field of nano-medicine, in particular to an anti-tumor nano-particle drug and a preparation method thereof. Background technique [0002] Malignant tumor is one of several major chronic diseases that endanger human health at present. Early detection, early diagnosis and early treatment are still the most effective means to prevent and control tumors. Unfortunately, most of the patients currently receiving clinical treatment are in the middle and late stages. Since its etiology, pathology, and pathogenesis have not been fully elucidated, the three major means of treating malignant tumors (radiotherapy, chemotherapy, and surgery) cannot cure most tumors. Therefore, various new treatment methods emerge in endlessly, such as interventional therapy. Minimally invasive therapy, biological targeted therapy, biological immunotherapy, etc., have failed to make breakthroughs. Therefore, it is the goal and responsibility of clinical ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/61A61K47/54A61K31/663A61K31/417A61P35/00
Inventor 蒋鸥孟凡智李富宇陈敬忠刘定荣汪勇蒋辉
Owner 蒋鸥
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