Anti-tumor prodrug having accurate structure and taking novel amphipathic polymer as carrier and synthetic method thereof

An amphiphilic polymer, anti-tumor drug technology, applied in anti-tumor drugs, pharmaceutical formulations, organic active ingredients, etc., can solve problems such as different lengths of chain segments

Inactive Publication Date: 2009-09-30
XIANGTAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the existing literature, aliphatic polyesters usually adopt the method of ring-opening polymerization of stannous octoate. By controlling the feed ratio, the molecular weight in the macroscopic range can be controlled. The molecular weight distribution is very narrow, but the length of the chain segment is different. Although these polymers Synthetic drug combinations are now used in clinical trials, and further pharmaceuticals are a huge challenge

Method used

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  • Anti-tumor prodrug having accurate structure and taking novel amphipathic polymer as carrier and synthetic method thereof
  • Anti-tumor prodrug having accurate structure and taking novel amphipathic polymer as carrier and synthetic method thereof
  • Anti-tumor prodrug having accurate structure and taking novel amphipathic polymer as carrier and synthetic method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Synthesis of polyethylene glycol 2000-succinic acid-glycolic acid octamer-paclitaxel

[0035] 1. Functionalization of Methoxylated Polyethylene Glycol

[0036]In a 100ml three-necked flask, equipped with a reflux condensing device and a magnetic stirrer, the baking reaction device was ventilated three times (high-purity argon), and under gas protection, 5g of terminal methoxypolyethylene glycol and pre-weighed D 1 g of dianhydride, and an equimolar amount of dimethylaminopyridine (DMAP), were added to 60 ml of anhydrous and oxygen-free tetrahydrofuran, and refluxed for 72 hours. After the reaction was completed, the solvent was concentrated, and then 10ml of 0.1M aqueous sodium bicarbonate solution was added to the residue, the filtrate was acidified with 10ml of 0.1M hydrochloric acid, the pH value of the solution was adjusted to 3-4 with hydrochloric acid, and then 100ml of ethyl acetate was used to Wash the water layer three times with ester, combine the ...

Embodiment 2

[0060] Example 2: Synthesis of polyethylene glycol 5000-succinic acid-glycolic acid octamer-paclitaxel

[0061] The reaction process is the same as in Example 1, but in the first step, in the there-necked flask of 100ml, a reflux condensing device and a magnetic stirrer are equipped, and the baking reaction device is ventilated three times (high-purity argon). Oxypolyethylene glycol, 1 g of succinic anhydride, and equimolar amounts of dimethylaminopyridine (DMAP) were added to 60 ml of anhydrous and oxygen-free tetrahydrofuran, and the mixture was refluxed for 72 hours. After the reaction was completed, the solvent was concentrated, and then 10ml of 0.1M aqueous sodium bicarbonate solution was added to the residue, the filtrate was acidified with 10ml of 0.1M hydrochloric acid, the pH value of the solution was adjusted to 3-4 with hydrochloric acid, and then 100ml of ethyl acetate was used to Wash the water layer three times with ester, combine the ethyl acetate solution and w...

Embodiment 3

[0062] Embodiment 3: Synthesis of polyethylene glycol 2000-diglycolic acid-glycolic acid octamer-paclitaxel

[0063] The reaction process is the same as in Example 1, but in the first step, in the there-necked flask of 100ml, a reflux condensing device and a magnetic stirrer are equipped, and the baking reaction device is ventilated three times (high-purity argon), and under gas protection, 5g polymer and 1 g of dihydroxyacetic anhydride, and an equimolar amount of dimethylaminopyridine (DMAP), added 60 ml of anhydrous and oxygen-free tetrahydrofuran, and refluxed for 72 hours. After the reaction was completed, the solvent was concentrated, and then 10ml of 0.1M aqueous sodium bicarbonate solution was added to the residue, the filtrate was acidified with 10ml of 0.1M hydrochloric acid, the pH value of the solution was adjusted to 3-4 with hydrochloric acid, and then 100ml of ethyl acetate was used to Wash the water layer three times with ester, combine the ethyl acetate soluti...

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Abstract

The invention discloses a prodrug system prepared by connecting a series of oligopolymers synthesized by a group protection and deprotection method and polyethyleneglycol to be used as a drug carrier, belonging to the technical field of chemical drugs. Laden drugs are water-insoluble anti-tumor drugs such as taxol, or other cancer therapy drugs such as doxorubicine and camptothecin. A research discovers that drug compositions prepared by the method greatly improve the hydrophobic nature of the anti-tumor drugs and can accurately control the gather time of the oligopolymers on focus parts and the hydrolyzation rupture time of ester bonds by accurately controlling the lengths of segmers of the oligopolymers so as to control the drug release time so that drugs are stably released, thereby the method prevents burst release causing toxic side effect on normal cells, reduces the drug dosage to enhance the curative effect and sufficiently plays a sustained and controlled release role; and in addition, the structure of the oligopolymers is accurate, and the molecular weight of synthesized amphipathic block polymers which are uniformly distributed is accurate, thereby the method can ensure synthesized drug ingredients to be definite and stable and the pharmacokinetics and the treatment effect (activity and toxicity) of the synthesized drugs to have good reproduction quality and be accurately defined.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, and relates to an antitumor prodrug and a synthesis method using a novel amphiphilic polymer with precise structure as a carrier. Background technique [0002] At present, the research on controlled release of drugs has become an important content of molecular engineering research on polymer biomaterials, as well as a very active fringe field in pharmacy and polymer chemistry. Generally, when polymers or other materials are used as drug carriers, as the drug content in the carrier decreases, the release rate of the drug also decreases, so the constant release of the drug cannot be guaranteed. However, when a biodegradable material is used as a drug carrier, as the carrier degrades in the body, the structure becomes looser, and the drug is more easily dissolved and diffused from the carrier, which coincides with the drug release caused by the reduction of the total drug content in the c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K47/34A61K45/00A61K31/337A61K31/4745A61K31/704A61P35/00A61K47/10A61K47/59A61K47/60
Inventor 张雪飞傅金燕钟冠群张海良
Owner XIANGTAN UNIV
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