Polyethylene glycol momomethyl ether-polycaprolactone-polyacrylic acid derivatives, and preparation and application thereof

A technology of monomethyl ether and polyethylene glycol, applied in the field of polyethylene glycol monomethyl ether-polycaprolactone-polyacrylic acid derivatives and their preparation and application, to improve solubility and oral bioavailability , to avoid the effect of degradation

Inactive Publication Date: 2011-02-16
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the solubility of a drug is often the limiting factor for its absorption in the gastrointestinal tract

Method used

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  • Polyethylene glycol momomethyl ether-polycaprolactone-polyacrylic acid derivatives, and preparation and application thereof
  • Polyethylene glycol momomethyl ether-polycaprolactone-polyacrylic acid derivatives, and preparation and application thereof
  • Polyethylene glycol momomethyl ether-polycaprolactone-polyacrylic acid derivatives, and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1: mPEG 5000 -Preparation of b-PCL-b-PAA block copolymer

[0060] Materials and Methods

[0061] ε-caprolactone (ε-CL): purchased from Sigma-Aldrich Shanghai Trading Co., Ltd., currently used in CaH 2 The reaction was carried out after drying in medium for 24 hours and distillation. Monomethyl ether of polyethylene glycol (mPEG): purchased from Sigma-Aldrich Shanghai Trading Co., Ltd., with a molecular weight of 5000 Da. Currently, the reaction is carried out after redistillation in freshly steamed toluene. Stannous octoate was purchased from Sigma-Aldrich Shanghai Trading Co., Ltd.

[0062] (1) Synthesis of mPEG-b-PCL block copolymer:

[0063] Using the ring-opening polymerization method, prepare mPEG with a mass ratio of 5:3, 5:5, 5:7 or 5:9, respectively 5000 -b-PCL. A) Take 5g of mPEG (5000Da) and 3g of ε-CL to prepare 5:3 mPEG 5000 -b-PCL; B) Take 5g of mPEG (5000Da) and 5g of ε-CL to prepare 5:5 mPEG 5000 -b-PCL; C) Take 5g of mPEG (5000Da) and 7g...

Embodiment 2

[0075] Example 2: mPEG 2000 -Preparation of b-PCL-b-PMAA block copolymer

[0076] Materials and Methods

[0077] ε-caprolactone (ε-CL): purchased from Sigma-Aldrich Shanghai Trading Co., Ltd., currently used in CaH 2 The reaction was carried out after drying in medium for 24 hours and distillation. Monomethyl ether of polyethylene glycol (mPEG): purchased from Sigma-Aldrich Shanghai Trading Co., Ltd., with a molecular weight of 5000 Da. Currently, the reaction is carried out after redistillation in freshly steamed toluene. Stannous octoate was purchased from Sigma-Aldrich Shanghai Trading Co., Ltd.

[0078] (1) Synthesis of mPEG-b-PCL block copolymer:

[0079] Using the ring-opening polymerization method, prepare mPEG with a mass ratio of 5:3, 5:5, 5:7 or 5:9, respectively 2000 -b-PCL. A) Take 5g of mPEG (2000Da) and 3g of ε-CL to prepare 5:3 mPEG 2000 -b-PCL; B) Take 5g of mPEG (2000Da) and 5g of ε-CL to prepare 5:5 mPEG 2000 -b-PCL; C) Take 5g of mPEG (2000Da) and 7...

Embodiment 3

[0088] Embodiment 3: Preparation of docetaxel polymer micelles by dialysis

[0089] Accurately weigh 50 mg successively to get the mPEG obtained in Example 1 5000 -b-PCL-b-PAA, each dissolved in 2ml tetrahydrofuran; at the same time, tetrahydrofuran was used as a solvent to configure a 1mg / mL docetaxel solution, and 2mL docetaxel solution was added to the configured polymer solution to obtain Drug carrier solution with a drug loading ratio of 4%. After 4 hours of magnetic stirring at room temperature, under strong stirring, 6 mL of redistilled water was added to the system at a rate of one drop per 10 seconds for hydration. After the addition was complete, the stirring was continued for 4 hours. In a dialysis bag, dialyze in double distilled water for 24 hours, and filter with a 0.45 μm microporous membrane after dialysis.

[0090] Table 3 for four different mPEG 5000 -Drug loading of b-PCL-b-PAA using dialysis method:

[0091] Table 3. Docetaxel mPEG 5000 -Drug loading o...

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Abstract

The invention belongs to the technical field of medicines, and relates to polyethylene glycol momomethyl ether-polycaprolactone-polyacrylic acid derivatives, and preparation and application thereof. The polyethylene glycol momomethyl ether-polycaprolactone-polyacrylic acid derivatives comprise polyethylene glycol momomethyl ether, polycaprolactone and polyacrylic acid derivatives with biocompatibility and biodegradability, and are prepared orderly by ring-opening polymerization and atom-transfer free radical polymerization. The obtained amphiphilic multipolymer can be self-assembled into micelle in water solution, and has certain response on the pH value of the environment. The medicine-carrying capacity and release behavior for the hydrophobic medicines can be changed by regulating the ratio of hydrophilic fragments to hydrophobic fragments and the length of the polyacrylic acid derivative fragment. The pH-sensitive micelle can be used as the carrier for oral administration of insoluble medicines to increase the solubility of liposoluble medicines in the human body gastrointestinal tract and avoid being damaged in the gastrointestinal tract, thereby enhancing the bioavailability.

Description

technical field [0001] The invention belongs to the field of new excipients and new dosage forms of pharmaceutical preparations, and relates to a pH-sensitive amphiphilic polymer polyethylene glycol monomethyl ether-polycaprolactone-polyacrylic acid derivative and its preparation and application. This kind of polymer can spontaneously form micelles in water, and due to the existence of pH-sensitive fragments, it has a certain response to the acidity and alkalinity in the gastrointestinal tract, so it can be used as a drug carrier for oral administration. Background technique [0002] Polymeric micelles are composed of amphiphilic polymers and are thermodynamically stable systems that spontaneously form when the concentration of amphiphilic polymers exceeds the critical micelle concentration (CMC). Depending on the structure and concentration of the polymer, it can have different morphologies. Generally speaking, the polymer micelle as a drug carrier has a typical core-shell ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00C08G63/664C08F8/12C08F293/00C08G63/91A61K47/32
Inventor 丁平田陈东梁慧敏
Owner SHENYANG PHARMA UNIVERSITY
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