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Method for preparing pH sensitive drug carrier micelle

A sensitive and drug-based technology, applied in drug combinations, pharmaceutical formulations, medical preparations of non-active ingredients, etc., can solve the problems of reduced water solubility of drug molecules, high synthesis costs, poor biocompatibility, etc., and achieve biocompatibility Good sex, less toxic and side effects, large load effect

Inactive Publication Date: 2015-02-11
CHENGDU LVKE HUATONG TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, due to the complex structure of the polymer in the star polymer, the prepared drug carrier has problems such as poor biocompatibility, decreased drug loading capacity, and reduced water solubility of drug molecules on the surface of dendrimer.
In addition, dendrimer has a complex structure and high synthesis cost
These problems limit the application of star-shaped polymer nano-drug delivery system

Method used

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  • Method for preparing pH sensitive drug carrier micelle
  • Method for preparing pH sensitive drug carrier micelle
  • Method for preparing pH sensitive drug carrier micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] ① Preparation of azide small molecule initiator

[0045] Step 1: Dissolve 5 mL of 2-chloroethoxyethanol in 25 mL of butanone, and add 4.5 g of NaN to the solution 3, 2.5gBu 4 NI, 10 mg of dicyclohexane-18-crown-6, the mixture was heated to boiling and stirred for 24 hours. The mixture was filtered and the precipitate was rinsed thoroughly with acetone. The resulting mixed solution is the crude product of the product, after the mixed solution was concentrated, at 90 o C was distilled to obtain the pure product. The resulting 2-azidoethoxyethanol 1 H NMR (CDCl 3 ): 3.70 (t, 2 H, C H 2 OH), 3.65 (t, 2 H, HOCH 2 C H 2 O), 3.56 (t, 2H, N 3 CH 2 C H 2 O), 3.37 (t, 2H, C H 2 N 3 ), and 2.56 (s, 1H, OH).

[0046] Step 2: Dissolve 2g of 2-azidoethoxyethanol and 5.09g of α-chloroacyl chloride in 30mL of dichloromethane prepared in step 1, transfer the reaction system to ice, and dissolve 6.8g of dicyclohexyl The carbodiimide was slowly added to the reaction ...

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Abstract

The invention discloses a method for preparing a pH sensitive drug carrier micelle. The method comprises the steps of: polymerizing phosphatidylcholine by using an atomic transfer radical polymerization method to obtain poly phosphatidylcholine; modifying the poly phosphatidylcholine by folate molecules; polymerizing benzyl glutamate carboxyanhydride by using a ring opening polymerization method to obtain poly(gamma-benzyl-L-glutamate); grafting adriamycin to poly(gamma-benzyl-L-glutamate) through a hydrazone bond; bonding the poly phosphatidylcholine and poly(gamma-benzyl-L-glutamate) via a click chemical method to obtain a block copolymer; respectively dissolving the block copolymer in tetrahydrofuran, transferring into a dialysis bag, and dialyzing by pure water, and filtering the dialysate by a dialysis membrane; and conducting freeze drying on the filtered solution, so as to obtain get the drug carrier micelle. The drug carrier micelle has a core-shell double-layer structure; and the outer layer is hydrophilic poly phosphatidylcholine, and the inner layer is a molecular drug coating. The material has the following advantages: the micelle belongs to nano particles, can realize targeting delivery of drug to cancer cells and pH sensitive release in cancer cell, and has large drug loading capacity and good stability; and the targeting function can effectively reduce the toxic and side effect of drugs on normal tissue and organs..

Description

technical field [0001] The invention relates to a preparation method of a pH-sensitive drug carrier micelle, in particular to a preparation method of a block polymer material drug carrier micelle with cancer cell targeting. The invention belongs to the field of polymer chemistry and polymer technology. Background technique [0002] Cancer has become the most important disease that endangers human health. One of the important methods to treat cancer is drug therapy. However, many anticancer drugs have defects such as insoluble in water and poor stability. For example, camptothecin, paclitaxel, doxorubicin, and 5-fluorouracil are difficult to be well utilized by organisms due to their poor solubility. Solving the problem of their water solubility is the key to the clinical application of such pharmaceutical preparations. In addition, most of the tumor treatment and diagnostic drugs have non-selective effects, and are often distributed in some normal tissues and organs, and th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/48A61K31/704C08G81/02A61P35/00
Inventor 周庆翰
Owner CHENGDU LVKE HUATONG TECH
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