Preparation method of block copolymer with dual responsiveness of rapid oxidization/reduction and selenium bonds and application of block copolymer

A block copolymer, responsive technology, applied in medical preparations containing active ingredients, medical preparations with inactive ingredients, drug combinations, etc., can solve the problems of rapid response and limited degree of dissociation of copolymer carriers

Active Publication Date: 2018-01-30
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the prior art, there have been some reports on fast oxidation / reduction sensitive polymers containing diselenide bonds, however, in these structures, limited diselenide bonds are only linked between longer different polymer blocks, As a drug carrier, the rapid response and degree of dissociation of copolymer carriers in vivo is very limited

Method used

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  • Preparation method of block copolymer with dual responsiveness of rapid oxidization/reduction and selenium bonds and application of block copolymer
  • Preparation method of block copolymer with dual responsiveness of rapid oxidization/reduction and selenium bonds and application of block copolymer
  • Preparation method of block copolymer with dual responsiveness of rapid oxidization/reduction and selenium bonds and application of block copolymer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Example 1: Diselenium small molecule capped by diazide group (N 3 -SeSe-N 3 )Synthesis

[0098] Diazide-terminated small diselenium molecules (N 3 -SeSe-N 3 ) is mainly prepared by two steps. The first step is to prepare the dichloro-capped small diselenium molecule (Cl-SeSe-Cl); the second step is to prepare the diazide-capped diselenium small molecule (N 3 -SeSe-N 3 ), the specific synthesis method is as follows:

[0099] Synthesis of dichloro-terminated diselenium small molecules (Cl-SeSe-Cl): put a 250 mL three-necked flask equipped with a stirring bar, an elbow, a constant pressure dropping funnel, and a plunger into an oven at 120 °C for 12 h, Take it out of the oven and put it in a desiccator before use, and wait until it cools down to room temperature before using it. Put the device on, blow nitrogen, and add 70 mL of anhydrous CH to the three-necked flask 2 Cl 2 , Weighed selenocystamine hydrochloride (1 g, 3.12 mmol) into a three-necked flask, and then...

Embodiment 2

[0101] Example 2: Synthesis of Dipropargyl-terminated Polyethylene Glycol (PA-PEG-PA)

[0102] Dipropargyl-terminated polyethylene glycol (PA-PEG-PA) is mainly prepared by a "one-pot method". The first step: use highly active KH to react with the terminal hydroxyl group of ethylene glycol to prepare an oxyanion initiator; the second step is to use the oxyanion initiator to react with 3-bromopropyne to prepare dipropargyl-terminated polyethylene Diol (PA-PEG-PA), the specific synthesis method is as follows:

[0103] Put the 100 mL branched flask equipped with a stirring bar, the constant pressure dropping funnel and the plunger into an oven at 120°C for 12 h to dry. Before use, take it out of the oven and put it in a desiccator, and wait until it cools down to room temperature before use. First, weigh HO-PEG-OH (5 g, 5 mmol) into a branched flask, then add 50 mL of toluene for azeotropic water removal, and repeat distillation twice. Then connect the branched flask to the double...

Embodiment 3

[0105] Embodiment three: two selenium-containing polyethylene glycol alternating copolymers (PA-PEG- alt -SeSe-PA) synthesis

[0106] The 50 mL branched flask equipped with a stirring bar was placed in an oven at 120 °C for 12 h to dry. Before use, it was taken out of the oven and cooled down to room temperature using a double-row pipe. Add CuBr (71.73 mg, 0.5 mmol), PMDETA (86.65 mg, 0.5 mmol) and 5 mL of anhydrous DMF, and stir well. Weigh PA-PEG-PA (281.5 mg, 0.25 mmol), N 3 -SeSe-N 3 (103.5 mg, 0.25 mmol) was put into a centrifuge tube, and 5 mL of anhydrous DMF was added to completely dissolve the two raw materials, then added to a branched flask, inflated and deflated three times and then sealed, transferred to a 35°C oil bath, and reacted for 24 h. To ensure that the polymer was terminated with propargyl groups, excess PA-PEG-PA (140.8 mg, 0.125 mmol) was added and the reaction was continued for 24 h.

[0107] After the reaction, pass the crude product over a neutr...

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Abstract

The invention discloses a preparation method of a block copolymer with dual responsiveness of rapid oxidization / reduction and selenium bonds and application of the block copolymer. The preparation method comprises the following steps: firstly preparing diazido-terminated double-selenium micromolecules (N3-SeSe-N3) and dipropargyl-terminated polyethylene glycol (PA-PEG-PA); obtaining alternating copolymer (PA-PEGalt-SeSe-PA) containing double selenium bonds and polyethylene glycol, wherein two ends of the alternating copolymer are terminated by alkynyl; then reacting the alternating copolymer (PA-PEGalt-SeSe-PA) with azido single-terminated polycaprolactone (PCL-N3) to obtain the block copolymer (PCL-PEGSeSe-PCL) with dual responsiveness of rapid oxidization / reduction and double selenium bonds; a nanoparticle self-assembled by the amphiphilic copolymer in an aqueous solution has high biocompatibility and biodegradability; the nanoparticle is coated with a hydrophobic anti-cancer drug; the polymer nanoparticle can be broken in the tumor cell environment for rapidly releasing the coated drug, so that the block copolymer has potential application prospects in the aspect of cancer therapy.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, and in particular relates to a preparation method of a fast oxidation / reduction dual-response block copolymer containing a diselenium bond and its application. Background technique [0002] Traditional nano-drug carriers are often prepared from non-degradable polymers, such as polyacrylic acid, polyethylene, polystyrene, and so on. These polymer carriers cannot be degraded after entering the body, are not easily excreted by the kidneys, and eventually remain and accumulate in the body, causing many side effects to patients in the long run. [0003] So far, polylactic acid (PLA), polyethylene glycol (PEG), polycaprolactone (PCL), polylactic-co-glycolic acid (PLGA), etc. have been approved by the U.S. Food and Drug Administration (FDA) for use in medical materials. Many nano drug carriers based on such polymers have been developed and applied. This kind of polymer material has good bi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00C08G63/08C08G65/337A61K9/51A61K47/34A61K31/704A61P35/00
CPCA61K9/5146A61K31/704A61P35/00C08G63/08C08G65/337C08G81/00
Inventor 倪沛红孙月何金林张明祖
Owner SUZHOU UNIV
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