Application of pH sensitive type amphiphilic graft polyphosphazene for preparing administration vesicle

A polyphosphazene and drug delivery technology, applied in pharmaceutical formulations, antitumor drugs, drug combinations, etc., can solve problems such as harsh conditions and medical application limitations, and achieve easy storage, high drug loading and encapsulation efficiency, and application. handy effect

Inactive Publication Date: 2011-03-16
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These pH-sensitive polymers used as drug carriers are almost all block copolymers, and their synthesis mainly adopts living polymerization reaction, which requires harsh conditions and often requires the use of considerable doses of heavy metals as catalysts. These problems greatly limit their medical applications.

Method used

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  • Application of pH sensitive type amphiphilic graft polyphosphazene for preparing administration vesicle
  • Application of pH sensitive type amphiphilic graft polyphosphazene for preparing administration vesicle
  • Application of pH sensitive type amphiphilic graft polyphosphazene for preparing administration vesicle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1p

[0058] Example 1 pH-responsive amphiphilic grafted polyphosphazene synthesis method

[0059] (1) Prepare poly(dichlorophosphazene) with aluminum chloride as catalyst

[0060] Weigh 4 g of chlorophosphazene cyclic trimer purified by sublimation and 0.2 g of anhydrous aluminum trichloride into a pre-cleaned and dried polymerization tube, vacuumize and seal the tube, carry out the polymerization reaction at 250°C for 5 hours, and wait for When the viscosity of the reactant remained almost constant, the polymerization was stopped and the polymerization tube was taken out to cool. Unseal the polymerization tube, add an appropriate amount of dry toluene solution to dissolve the reactants. After dissolution, it was precipitated with petroleum ether and dried in vacuum to obtain a white elastomer, that is, poly(dichlorophosphazene).

[0061] (2) Synthesis of pH-responsive amphiphilic grafted polyphosphazene copolymers via stepwise nucleophilic substitution reactions

[0062] Dissol...

Embodiment 2p

[0065] Example 2 pH-responsive amphiphilic grafted polyphosphazene synthesis method

[0066] (1) The preparation of poly(dichlorophosphazene) is the same as in Example 1.

[0067] (2) In addition to slowly adding 3.4g NH 2 50ml of THF solution containing PEG (molecular weight is 2000) and 0.23ml TEA, 10ml of THF solution containing 0.35g N,N-diisopropylethylenediamine (DPA) and 0.3ml TEA, and 3.0g ethyl p-aminobenzoate Except for 10 milliliters of THF solution of ester (EAB) and 2.5 ml TEA, all the other operations were the same as step (2) in Example 1 to obtain pH-responsive amphiphilic grafted polyphosphazene copolymer P2.

[0068] In the copolymer P2, the mass percentage of the first grafting group, that is, the amino-terminated polyethylene glycol of the hydrophilic segment, is 48%, and the second grafting group, that is, N-[2-(N', N'-two Isopropylamino) ethyl] the mass percentage of amino is 5%, and the mass percentage of N-(benzoic acid ethyl group)-4-amino is 41% in ...

Embodiment 3

[0069] Example 3 Preparation of administration vesicles

[0070] (1) Preparation and characterization of P1 polymer drug-loaded vesicles

[0071]Dissolve 30 mg of the pH-responsive amphiphilic graft polyphosphazene copolymer P1 prepared in Example 1 in 5 ml of N,N-dimethylformamide together with 6 mg of doxorubicin, and stir at a speed of 0.3 ml / min under magnetic stirring 5ml of pure water was slowly added dropwise therein, and the obtained solution was loaded into a dialysis bag with a molecular weight cut-off of 14000 Da, dialyzed in pure water for two days to remove N, N-dimethylformamide, and then filtered with a 0.45 μm filter membrane to obtain a clear solution that was It is an aqueous dispersion of pH-responsive amphiphilic grafted polyphosphazene doxorubicin administration vesicles (P1-DOX).

[0072] The above aqueous dispersion is freeze-dried to obtain a pH-responsive polyphosphazene-loaded doxorubicin vesicle freeze-dried powder.

[0073] The particle size of th...

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Abstract

The invention discloses an application of pH sensitive type amphiphilic graft polyphosphazene for preparing a pH response type amphiphilic graft polyphosphazene administration vesicle. The administration vesicle contains pH response type amphiphilic graft polyphosphazene and drugs, wherein metered by the total weight of the drugs and the pH response type amphiphilic graft polyphosphazene, the weight percent of the drugs is 0.001%-30%, and the weight percent of the pH response type amphiphilic graft polyphosphazene is 70%-99.999%. The pH response type amphiphilic graft polyphosphazene is a graft polymer which is characterized in that a polyphosphazene chain segment is taken as a framework, a first graft group and a second graft group are connected on a phosphorus atom, and a third graft group is selectively connected on the phosphorus atom. The administration vesicle can load one or two water-soluble drugs and hydrophobic drugs, has pH responsiveness in drug release, can quickly release drugs near tumor tissues or in tumor cells at the fixed time, and has a function of reversing the multidrug resistance of tumor cells.

Description

technical field [0001] The invention relates to a drug release system, in particular to the application of a pH-sensitive amphiphilic grafted polyphosphazene in the preparation of a pH-responsive amphiphilic grafted polyphosphazene drug delivery vesicle, which can be loaded with hydrophobic Drug or hydrophilic drug or both hydrophobic and hydrophilic drug loading. Background technique [0002] Simultaneous use of multiple drugs is a common approach in antitumor therapy, but different drugs are likely to have great differences in solubility properties (hydrophilicity). Some nano-drug carriers commonly used in clinical and research do not have the ability to simultaneously load two or more drugs with different hydrophilicity and hydrophobicity in large quantities. For example, solid nanoparticles are mostly prepared by biodegradable polymer materials or higher fatty acids, and the loading capacity of water-soluble drugs is poor, and they are easily taken up by endothelial-ric...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/19A61K47/34A61P35/00
Inventor 邱利焱郑程
Owner ZHEJIANG UNIV
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