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Preparation method of enzymatic cross-linking medicine carrying nano micelle

A drug-loading nanometer and micelle technology, which is applied in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc. Fast cross-linking effect

Active Publication Date: 2015-06-17
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The object of the present invention is to provide a kind of preparation method of enzymatic cross-linking drug-loaded nano-micelle aiming at the potential toxicity existing in the traditional cross-linking method and the problem that the operation is not easy enough, the preparation method utilizes horseradish peroxidase, Compared with the traditional cross-linking method, it has the advantages of safety, non-toxicity, easy operation and fast cross-linking, and has good biomedical application prospects.

Method used

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  • Preparation method of enzymatic cross-linking medicine carrying nano micelle
  • Preparation method of enzymatic cross-linking medicine carrying nano micelle
  • Preparation method of enzymatic cross-linking medicine carrying nano micelle

Examples

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Embodiment 1

[0032] A preparation method of enzymatically cross-linked drug-loaded nano micelles, comprising the steps of:

[0033] 1) Preparation of N-p-hydroxyphenylethylacrylamide (NHPAAm)

[0034] Add 1.0 g of tyramine hydrochloride to a 100 mL dry three-necked flask, add DMF to dissolve, protect with nitrogen, add 2.5 mL of triethylamine, and place in an ice-water bath. Add 0.78 g of acryloyl chloride dropwise, stir overnight, naturally warm to room temperature, filter, rotary evaporate, dissolve in ethyl acetate, wash with saturated brine for 3 times, remove water, concentrate, and purify on a silica gel column to obtain white solid N-p-hydroxybenzene Ethylacrylamide monomer.

[0035] 2) Preparation of methoxypolyethylene glycol 3-benzyl trithioester propionate (PEG-BSPA)

[0036] Add 5 g of polyethylene glycol monomethyl ether (mPEG) with a molecular weight of 5000 (1 mmol, 1 e.q.), 0.54 g of 3-benzylsulfanyl thiocarbonyl sufanyl propionic acid into a 250 mL single-necked flask ,...

Embodiment 2

[0056] A method for preparing enzymatically cross-linked drug-loaded nanomicelles, the steps of preparing a series of nanomicelles are basically the same as in Example 1, the difference is that the drug loaded is paclitaxel, wherein the nanomicelles loaded with paclitaxel are prepared As an example to illustrate its preparation method:

[0057] Mix 2 mL of polymer aqueous solution with a concentration of 2 mg / mL, 2 mL of HRP aqueous solution with a concentration of 250 U / mL, and 0.5 mL of paclitaxel with a concentration of 0.1 mg / mL in acetone, then heat up to 37 °C, stir overnight and promote the full volatilization of acetone. Add 1 mL of 10wt% aqueous hydrogen peroxide dropwise in batches, stir for 8-10 hours, and dialyze for two days to obtain paclitaxel-encapsulated enzymatically cross-linked drug-loaded nanomicelles.

Embodiment 3

[0059] A method for preparing enzymatically cross-linked drug-loaded nano-micelles. The steps for preparing a series of nano-micelles are basically the same as in Example 1, except that the drug loaded is camptothecin, and the nano-micelles loaded with paclitaxel are prepared. Take micelles as an example to illustrate its preparation method

[0060] Mix 2mL of polymer aqueous solution with a concentration of 2mg / mL, 2mL of HRP aqueous solution with a concentration of 250 U / mL, and 0.5 mL of paclitaxel in acetone with a concentration of 0.1 mg / mL, heat up to 30-40°C (take a single value), and stir After 8-10 hours, 1 mL of 10wt% hydrogen peroxide aqueous solution was added dropwise in batches, stirred for 8-10 hours, and dialyzed for two days to obtain enzymatically cross-linked drug-loaded nanomicelles loaded with camptothecin.

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Abstract

The invention relates to a preparation method of an enzymatic cross-linking medicine carrying nano micelle. The preparation method comprises the following steps: carrying out self-assembling to prepare a polymer micelle system by using a thermosensitive amphiphilic block copolymer, introducing a phenol group capable of generating cross-linking reaction into a thermosensitive block, catalyzing peroxidized hydroxide phenol group by Peroxidase to generate cross-linking reaction to obtain a nuclear crosslinking polymeric micelle, wherein the lowest critical micelle concentration is remarkably lower than that of nano micelle which is not cross-linked; when the micelle is prepared, adding adriamycin, taxol or camptotheca acuminate to prepare the enzymatic cross-linking medicine carrying nano micelle. The preparation method provided by the invention has the advantages that compared with conventional cross-linking methods, the preparation method has the advantages of safety, no toxicity, quick cross linking and the like, and is simple and convenient to operate, and has a good application prospect; the enzymatic cross-linking medicine carrying nano micelle has lower critical micelle concentration, so that the stability is improved, the circulating time of the micelle in blood can be prolonged and the efficiency that the micelle is endocytosed by tumor cells is increased, thereby further improving the bioavailability and the therapeutic effect of the medicine.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a method for preparing enzymatically cross-linked drug-loaded nano micelles. Background technique [0002] Compared with traditional small-molecule drugs, the nano drug delivery system can deliver the drug to the lesion at a fixed point and time, reduce its systemic distribution and dosage, improve the utilization rate of the drug, and reduce the side effects. [0003] At present, nano drug delivery systems mainly include polymer nanoparticles (vesicles and micelles, etc.), prodrugs coupled to polymers, inorganic and metal nanoparticles, etc. Among them, the construction of nanoparticles, especially polymer micelles, based on the self-assembly behavior of polymers is an important research field. Usually, the structure of micelles obtained by self-assembly is not stable enough, and will be greatly diluted when it enters the blood circulation, leading to early leakage of drugs...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/32A61K31/337A61K31/4745A61K31/704C08F293/00C08F220/58C08F220/54A61P35/00
Inventor 袁直吴玉昆赖全勇赖舒琦王蔚
Owner NANKAI UNIV
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