ph responsive polymer mixed micelle and application thereof

A technology for mixing micelles and polymers, which can be used in drug combinations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc. It can solve the problems of sudden release, failure to achieve performance, and disintegration of micelles.

Inactive Publication Date: 2015-07-08
GUANGDONG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patented technology allows for create a stable mixture containing both an active ingredient (such as chemotherapy) or other substances that have specific functions within them called pharmaceutical agents. These mixtures provide improved loading capabilities compared to existing formulations while also being able to control their releasing rate over times by changing factors like pH levels inside the patient's bloodstream. Additionally, this new type of material has potential uses in delivering various types of medications such as antiinflammatory compounds through liposomes filled into tiny holes on top of biodegradable microparticles made from synthetic resin particles.

Problems solved by technology

Technologies aim at developing improved systems containing small particles called quantum dots, such as colloidal gold clusters, loaded onto biodegradable matrices like polysaccharides. These tiny particles exhibited various advantages over traditional methods including low dosage requirements, easy handling during manufacturing processes, long retention times without releasing after being implanted within tissues due to enzyme responses caused by inflammations associated with disease states. Additionally, these techniques involve mixing specific types of polymers together, allowing each component to interact differently depending upon its needs.

Method used

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  • ph responsive polymer mixed micelle and application thereof
  • ph responsive polymer mixed micelle and application thereof
  • ph responsive polymer mixed micelle and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Synthesis of brominated polyethylene glycol (MPEG-Br): Weigh MPEG (5g, Mn=5000) and add the solvent into a dry 100ml anhydrous and oxygen-free reaction bottle, seal it with a reverse rubber stopper, and vacuumize - After blowing nitrogen gas for 3 times, under the protection of nitrogen gas, add the dehydrated solvent dichloromethane (30ml) and dehydrated triethylamine (TEA, 0.5ml) sequentially with a syringe, and then cool to 0°C in an ice bath, Slowly add 2,4-dibromoisobutyryl bromide (NA, 0.5ml) dropwise under stirring conditions, react at 0°C for 2h after the dropwise addition, then raise the temperature to 40°C, continue the reaction for 12h, after the reaction Wash with dilute hydrochloric acid and pure water three times respectively, drop the organic phase into 0°C n-hexane of ten times its volume to precipitate, filter, and finally vacuum-dry at 40°C for 48 hours.

Embodiment 2

[0078] Synthetic MPEG-b-PDEAEMA 20 :

[0079] The pH responsive monomer DEAEMA (1.43g), MPEG-Br (2g), catalyst CuBr 2 (2.78mg) and solvent were added to a 150ml anhydrous and oxygen-free reaction bottle, sealed with a reverse rubber stopper, vacuumed-nitrogen three times, under the protection of nitrogen, added THF (35ml) to remove water with a syringe in turn, and prepared Body PMDETA (33.64mg) and reducing agent Sn(Oct) 2 (78.6 mg), after freezing in liquid nitrogen, vacuumize and blow nitrogen three times, stir for 15 minutes after thawing, then start to heat up, and react in an oil bath at 65°C for 24 hours. After most of THF was removed by rotary evaporation under reduced pressure, the organic phase was slowly added dropwise to 200ml of cold n-hexane to precipitate, filtered, and finally vacuum-dried at 45°C for 48h, Mn=9075.8, PDI=1.047.

Embodiment 3

[0081] Synthetic MPEG-b-PDEAEMA 35 :

[0082] The pH responsive monomer DEAEMA (2.5185g), MPEG-Br (2g), catalyst CuBr 2 (10.5mg) and solvent were added to a 150ml anhydrous and oxygen-free reaction bottle, sealed with a reverse rubber stopper, vacuumed-nitrogen three times, under the protection of nitrogen, add dehydrated toluene (30ml) with a syringe in turn, and prepare Body PMDETA (42.34mg) and reducing agent Sn(Oct) 2(89.6 mg), after freezing in liquid nitrogen, vacuumize and blow nitrogen three times, stir for 15 minutes after thawing, then start to heat up, and react in an oil bath at 80°C for 12 hours. After most of the toluene was removed by rotary evaporation under reduced pressure, the organic phase was slowly added dropwise to 200ml of cold n-hexane to precipitate, filtered, and finally vacuum-dried at 45°C for 48h, Mn=11098, PDI=1.054.

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Abstract

The invention relates to a pH responsive polymer mixed micelle and application thereof and belongs to the technical field of medicinal functional carrier materials. the mixed micelle is prepared by mixing two polymers (MPEG-b-PDEAEMA and MPEG-b-PCL) with a hydrophobic anti-tumor drug according to a certain ratio, wherein the MPEG-b-PDEAEMA is prepared by the following steps: bromizing a hydrophilic block mono methyl polyethylene glycol MPEG; and then introducing methacrylic acid (N, N)-diethylamino ethyl ester (serving as a pH responsive block) into a polymer; and the MPEG has pH responsiveness; the other polymer MPEG-b-PCL is prepared by carrying out ring opening polymerization on a hydrophilic block (epsilon)-caprolactone under the direct initiating effect of the hydrophilic block mono methyl polyethylene glycol MPEG, and MPEG-b-PCL is amphiphilic. The mixed polymer micelle is amphiphilic and has pH responsiveness, the drug loading amount of hydrophilic anti-tumor drug can reach up to 26.79%, and the micelle has a good pH control release effect, so that the drug stably exists for a long time in a neutral pH condition and the drug is released at a space velocity in an acidic pH condition. In addition, the synthetic routes and preparation methods of the two polymers are quite short.

Description

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Claims

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Application Information

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Owner GUANGDONG UNIV OF TECH
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