Preparation of poly(L-glutamic acid)-b-polyethylene glycol medicine carrying nano micelle

A drug-loaded nano-polyethylene glycol technology, which is applied to medical preparations containing non-active ingredients, medical preparations containing active ingredients, and anti-tumor drugs, etc., to achieve prolonged maintenance of drug efficacy, significant reduction responsiveness, and easy absorption Effect

Active Publication Date: 2015-08-26
南京邦鼎生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the research on the encapsulation and triggered release of anti-tumor drugs by this kind of stimuli-responsive polymer micelles with cross-linked structure is still in the early stage, but it will surely bring new breakthroughs in the diagnosis and treatment of tumors and other diseases

Method used

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  • Preparation of poly(L-glutamic acid)-b-polyethylene glycol medicine carrying nano micelle
  • Preparation of poly(L-glutamic acid)-b-polyethylene glycol medicine carrying nano micelle
  • Preparation of poly(L-glutamic acid)-b-polyethylene glycol medicine carrying nano micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: Preparation of sulfhydryl-terminated poly(L-glutamic acid-γ-benzyl ester)

[0019] In a three-necked flask replaced with nitrogen beforehand, mercaptoethylamine (AET) and BLG-NCA with a molar feed ratio of 1:40 were sequentially added, and the two were dissolved in methylene chloride solvent to make the total concentration of reactants 10w%. Stir magnetically for 72 hours at room temperature in a nitrogen atmosphere, concentrate the reaction solution, and drop it into excess butyl acetate, ice bath for half an hour to obtain a flocculent precipitate, centrifuge to obtain a pale yellow precipitate, and vacuum dry at 35°C to obtain terminal sulfhydryl groups Poly(L-glutamic acid-γ-benzyl ester), referred to as PLT.

Embodiment 2

[0020] Example 2: Preparation of poly(L-glutamic acid-γ-benzyl ester)-b-polyethylene glycol

[0021] PLT and polyethylene glycol methacrylate (MAPEG) are co-dissolved in DMF solution. The molecular weight of polyethylene glycol methacrylate is M n =475g / mol, the molar ratio of PLT to polyethylene glycol methacrylate is 1:1~1:1.5, the two are dissolved in DMF solvent, the total concentration of reactants is 15w%, and the total weight of reactants is 1 % AIBN is the initiator. Free radical polymerization is carried out at 60℃. After 24 hours, the reaction solution is added dropwise to ultrapure water to obtain a milky white turbid liquid, which is transferred to a dialysis bag with a molecular weight cut-off of 3500 for 72 hours. Change the water every 12 hours, and finally freeze-dry the product to obtain a pale yellow solid poly(L-glutamic acid-γ-benzyl ester)-b-polyethylene glycol, abbreviation: PLE;

Embodiment 3

[0022] Example 3: Crosslinking of micelles

[0023] The PLE obtained in Example 2 and cystamine were mixed and added to the DMF solvent. The cystamine and PLE were fed at a molar ratio of 1:1, 2:1, 4:1, and the total concentration of the two dissolved in the DMF solvent was 12w. %, magnetically stirred at 30℃ for 5h and then cooled to room temperature, take the reaction solution, add ultrapure water dropwise to it and stir until there is obvious Tyndall effect, dialyze with a dialysis bag with molecular weight cut off of 3500 for 72h and freeze-dry , Then prepare a micelle solution with a concentration of 0.8w% for use; prepare a series of crosslinked micelles with different crosslinking degrees according to the above ratio. See synthetic route figure 1 .

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Abstract

The invention firstly adopts mercaptoethylamine to trigger ring opening polymerization of L-glutamic acid-gamma-benzyl ester-N-carboxylic acid anhydride (BLG-NCA) to prepare mercaptyl-terminated (L-glutamic acid-gamma-benzyl ester) polymer, the mercaptyl-terminated (L-glutamic acid-gamma-benzyl ester) polymer is used as a macromolecular chain transfer agent to perform free radical polymerization with activated monomer polyethylene glycol metacrylic acid ester (MAPEG, Mn is equal to 475g / mol), and thereby amphiphilic poly(L-glutamic acid)-b-polyethylene glycol is obtained; cystamine is used for crosslinking L-glutamic acid-gamma-benzyl ester therein, meanwhile the residual gamma-benzyl ester groups are converted into carboxylic acid groups and adriamycin amycin is statically loaded, and thereby the nano micelle is formed by self-assembling in aqueous solution.

Description

Technical field [0001] A preparation of poly(L-glutamic acid)-b-polyethylene glycol drug-loaded nano micelles belongs to the technical field of biological materials and sustained release. Background technique [0002] The special core-shell structure of polymer micelles can be used as a micro-memory for anti-tumor drugs, and is an ideal drug release system. However, traditional polymer micelles lack the function of recognizing and responding to tumor cells, so they cannot release drugs quickly and timely at the tumor site, and the therapeutic effect is not good. There are very few examples that can be applied to the clinic. It also has problems such as being unable to maintain its own stability when responding to changes in the temperature and pH factors of the surrounding environment; at the same time, the micelles will disintegrate after being highly diluted by body fluids after oral or injection into the body. The leakage of medicine. With the rapid rise of interdisciplinary...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K31/704A61K47/48A61P35/00C08G69/08C08G81/00C08F293/00
Inventor 倪才华杨期颐张丽萍石刚
Owner 南京邦鼎生物科技有限公司
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