A polymeric chloroquine fluorenylmethylcarbonyl nanogel delivery system and preparation method thereof

A technology of chloroquine fluorenylmethylcarbonyl nanometer and chloroquine fluorenylmethyl carbonyl, which is applied in the field of pharmaceutical preparations and can solve the problems of insignificant treatment effect of malignant advanced tumors and no anti-tumor metastasis function.

Active Publication Date: 2022-03-25
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, since nanogels mostly use traditional gel materials and do not have anti-tumor metastasis function, the therapeutic effect on malignant advanced tumors is not significant. Therefore, it is urgent to seek innovative nanogel modification strategies for malignant advanced tumors.

Method used

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  • A polymeric chloroquine fluorenylmethylcarbonyl nanogel delivery system and preparation method thereof
  • A polymeric chloroquine fluorenylmethylcarbonyl nanogel delivery system and preparation method thereof
  • A polymeric chloroquine fluorenylmethylcarbonyl nanogel delivery system and preparation method thereof

Examples

Experimental program
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Embodiment 1

[0039] Preparation method of polymerized chloroquine-fluorenylmethylcarbonyldextrin nanogel drug loading system

[0040] Step 1, preparation of hydroxychloroquine: dissolve 0.6 g of hydroxychloroquine sulfate in 2 mL of pure water, under constant stirring, add excess 30% ammonia water until the white insoluble product does not continue to increase, add dichloromethane to extract 4 -6 times, collect the organic phase and add an appropriate amount of anhydrous sodium sulfate overnight, and evaporate the solvent under reduced pressure to obtain the final desalted product.

[0041] Step 2, synthesis of fluorenylmethylcarbonyldextrin: dissolve 210 mg of dextrin in 2 mL of dimethylformamide, add 206 mg of dicyclohexylcarbodiimide, 24 mg of 4-dimethylaminopyridine and 297 mg Fmoc-glycine, react for 12-24 h under an inert gas environment, after removing insolubles, add the reaction solution to 10 times the volume of anhydrous ether, centrifuge at 3000 rpm for 3 min, discard the supern...

Embodiment 2

[0047] Preparation method of polymerized chloroquine-fluorene methyl carbonyl dextran nanogel drug loading system

[0048] Step 1, preparation of hydroxychloroquine: dissolve 0.6 g of hydroxychloroquine sulfate in 2 mL of pure water, under constant stirring, add excess 30% ammonia water until the white insoluble product does not continue to increase, add dichloromethane to extract 4 -6 times, collect the organic phase and add an appropriate amount of anhydrous sodium sulfate overnight, and evaporate the solvent under reduced pressure to obtain the final desalted product.

[0049] Step 2, Synthesis of Fluorenylmethylcarbonyl Dextran (HF): Dissolve 164 mg of dextran in 2 mL of dimethylformamide, add 206 mg of dicyclohexylcarbodiimide, 24 mg of 4-dimethylformamide respectively Aminopyridine and 297 mg Fmoc-glycine were reacted under an inert gas environment for 12-24 h. After removing insolubles, the reaction solution was added to 10 times the volume of anhydrous ether, centrifug...

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Abstract

The invention discloses a polymerized chloroquine fluorenylmethylcarbonyl nanogel delivery system, the delivery system comprises polymerized chloroquine fluorenylmethyl nanogel particles and anti-tumor drugs wrapped in the particles; the nanogel particles are composed of The polysaccharide main chain modified with hydroxychloroquine and fluorenylmethoxycarbonyl is formed by cross-linking. The molecular weight of the polysaccharide main chain is 5-100 kD. The molar substitution degree of hydroxychloroquine on the polysaccharide main chain is 5%-50%. The molar substitution degree of the methoxycarbonyl group on the polysaccharide main chain is 1%-30%. The polymerized chloroquine fluorenylmethylcarbonyl nanogel delivery system of the present invention can inhibit the level of intracellular autophagy and block the signal pathway of tumor cell metastasis, and at the same time, carry the anti-tumor drug paclitaxel through π-π conjugation, and achieve a two-pronged approach to malignancy. Tumor metastasis and proliferation.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a polymerized chloroquinefluorenylmethylcarbonyl nanogel delivery system and a preparation method thereof. Background technique [0002] In China, the incidence of tumors has increased significantly in recent years, and most of them are patients with malignant tumors. The metastasis of malignant tumor cells significantly increases the mortality rate of patients. Paclitaxel, a traditional chemotherapeutic drug, binds to intracellular tubulin and hinders the dissociation of microscopic proteins, thereby blocking cell mitosis and promoting tumor cell apoptosis, bringing hope for tumor therapy. However, due to the extremely low water solubility of paclitaxel, the traditional paclitaxel injection requires a mixed solution of polyoxyethylene castor oil and anhydrous ethanol as a solubilizer, but polyoxyethylene castor oil will bring a series of allergic ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K31/337A61K31/438A61K47/54A61P35/00A61P35/04
CPCA61K9/0019A61K47/6939A61K31/337A61P35/00A61P35/04A61K31/438A61K47/542A61K2300/00
Inventor 孙敏捷董婧雯
Owner CHINA PHARM UNIV
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