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Temperature-sensitive organic/inorganic hybrid block copolymer, and preparation method and application thereof

A technology of temperature-sensitive block copolymers, which is applied in the field of copolymers, can solve the problems of toxic side effects of normal cells and tissues, cannot meet the needs of medical polymers, and affect the degree of drug release control and the accuracy of in vivo positioning and release. Sensitivity, accuracy of high in vivo localized release, effect of high degree of control

Inactive Publication Date: 2015-06-03
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This star-shaped block copolymer containing POSS can form nano micelles in water and has temperature-controlled release characteristics, but there are following disadvantages in this star-shaped block copolymer containing POSS: 1. This polymer does not have a prominent Therefore, it directly affects the control degree of drug release and the accuracy of localized release in vivo
2 The preparation method adopts atom transfer radical polymerization (ATRP), so there will be a small amount of heavy metal salt residue, which has toxic side effects on normal cells and tissues
3 This block copolymer can only load hydrophobic drugs, which cannot meet the current demand for medical polymers that simultaneously load and release hydrophilic and hydrophobic drugs

Method used

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  • Temperature-sensitive organic/inorganic hybrid block copolymer, and preparation method and application thereof
  • Temperature-sensitive organic/inorganic hybrid block copolymer, and preparation method and application thereof
  • Temperature-sensitive organic/inorganic hybrid block copolymer, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] 1 Preparation of macromolecular chain transfer agent

[0026] MAPOSS (1.846g, 1.96mmol), CDB (49mg, 0.18mmol) and AIBN (1.8mL×5×10 -3 M, 0.009mmol) was dissolved in toluene (0.7mL). After continuous freeze-thaw degassing for 3-5 times, it was polymerized at 65°C under the protection of argon. After a fixed reaction time, it was quenched with liquid nitrogen to stop the reaction. Using methanol / ethyl acetate=6 / 1 as the precipitating agent, the precipitation was repeated 3 times to obtain a macromolecular chain transfer agent whose degree of polymerization is 10, that is, PMAPOSS 10 .

[0027] 2 Preparation of temperature-sensitive organic / inorganic hybrid block copolymers

[0028] PMAPOSS 10 (0.3478g, 2×10 -5 mol), NIPAM (0.4068g, 3.6×10 -3 mol), OEGMA (0.176g, 4×10 -4 mol) and AIBN (0.0007g, 4×10 -6 mol) was dissolved in tetrahydrofuran (15mL), after continuous freeze-thaw degassing for 3 to 5 times, it was polymerized at 65°C under the protection of argon, and t...

Embodiment 2

[0034] 1 Preparation of macromolecular chain transfer agent

[0035] MAPOSS (1.846g, 1.96mmol), CDB (49mg, 0.18mmol) and AIBN (1.8mL×5×10 -3 M, 0.009mmol) was dissolved in toluene (0.7mL). After continuous freeze-thaw degassing for 3 to 5 times, it was polymerized at 65°C under the protection of argon. After a fixed reaction time, it was quenched with liquid nitrogen to stop the reaction. Using methanol / ethyl acetate=6 / 1 as the precipitating agent, the precipitation was repeated 3 times to obtain a macromolecular chain transfer agent whose degree of polymerization is 10, that is, PMAPOSS 10 .

[0036] 2 Preparation of temperature-sensitive organic / inorganic hybrid block copolymers

[0037] PMAPOSS 10 (0.3478g, 2×10 -5 mol), NIPAM (0.452g, 4×10 -3 mol), OEGMA (0.132g, 3×10 -4 mol) and AIBN (0.0007g, 4×10 -6 mol) was dissolved in tetrahydrofuran (15mL), after continuous freeze-thaw degassing for 3 to 5 times, it was polymerized at 65°C under the protection of argon, and t...

Embodiment 3

[0043] 1 Preparation of macromolecular chain transfer agent

[0044] MAPOSS (1.846g, 1.96mmol), CDB (49mg, 0.18mmol) and AIBN (1.8mL×5×10 -3 M, 0.009mmol) was dissolved in toluene (0.7mL). After continuous freeze-thaw degassing for 3 to 5 times, it was polymerized at 65°C under the protection of argon. After a fixed reaction time, it was quenched with liquid nitrogen to stop the reaction. Using methanol / ethyl acetate=6 / 1 as the precipitating agent, the precipitation was repeated 3 times to obtain a macromolecular chain transfer agent whose degree of polymerization is 10, that is, PMAPOSS 10 .

[0045] 2 Preparation of temperature-sensitive organic / inorganic hybrid block copolymers

[0046] PMAPOSS 10 (0.3478g, 2×10 -5 mol), NIPAM (0.5424g, 4.8×10 -3 mol), OEGMA (0.132g, 3×10 -4 mol) and AIBN (0.0007g, 4×10 -6 mol) was dissolved in tetrahydrofuran (15mL), after continuous freeze-thaw degassing for 3 to 5 times, it was polymerized at 65°C under the protection of argon, an...

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Abstract

The invention relates to a copolymer, particularly a temperature-sensitive organic / inorganic hybrid block copolymer, and a preparation method and application thereof. The temperature-sensitive organic / inorganic hybrid block copolymer is PMAPOSSn-b-P(NIPAMp-co-OEGMAq). The preparation method comprises the following steps: dissolving MAPOSS, an initiator and a chain-transfer agent in a solvent, carrying out freezing-defreezing circulation to remove oxygen, and reacting in an inert gas atmosphere; after the reaction finishes, adding the solution into a precipitating agent, and drying to obtain a macromolecular chain-transfer agent PMAPOSS; dissolving the macromolecular chain-transfer agent PMAPOSS, an initiator, NIPAM and OEGMA in a solvent, carrying out freezing-defreezing circulation to remove oxygen, and reacting in an inert gas atmosphere; and after the reaction finishes, adding the solution into a precipitating agent, and drying to obtain the temperature-sensitive organic / inorganic hybrid block copolymer. The invention has wide application prospects in the aspects of preparation of drug carriers, targeted therapy and the like.

Description

technical field [0001] The invention relates to a copolymer, in particular to a temperature-sensitive organic / inorganic hybrid block copolymer with excellent biocompatibility and high temperature sensitivity, as well as its preparation method and application. Background technique [0002] Smart polymers, especially those sensitive to pH and temperature, have been widely used in the fields of medicine and biology in recent years due to their good biocompatibility, especially in oral targeted drug delivery systems. received widespread attention. [0003] Poly(N-isopropylacrylamide) (PNIPAM) and polyethylene glycol (PEG) are typical temperature-sensitive polymers, which have been applied in the fields of controlled release of biopharmaceuticals. However, pure PNIPAM or PEG has the disadvantages of low mechanical strength and poor thermal stability. Polyhedral Oligomeric Silsesquioxane (Polyhedral Oligomeric Silsesquioxane, referred to as POSS), the molecular size is between 1...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08F220/54C08F220/28C08F230/08C08F2/38A61K47/32
Inventor 许一婷谢剑杰戴李宗高辉陈国荣罗健龙曾碧榕罗伟昂
Owner XIAMEN UNIV
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