Gel medicine sustained release preparation based on hydrophobically modified gemcitabine derivative as well as preparation method and application of gel medicine sustained release preparation

A technology of gemcitabine and hydrophobic modification, applied in the field of drug preparation, can solve the problems of reducing the bioavailability of drugs, unable to obtain anti-tumor effect, etc., and achieve the effects of improving in vivo stability, simple and practical preparation process, and convenient practical operation and application.

Inactive Publication Date: 2020-05-08
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Gemcitabine is a small hydrophilic molecule. If it is simply mixed into the PEG / polyester hydrogel system, it will cause its initial burst release due to the rapid diffusion of the drug, which not only reduces the bioavailability of the drug, but also cannot be obtained. Long-lasting anti-tumor effect

Method used

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  • Gel medicine sustained release preparation based on hydrophobically modified gemcitabine derivative as well as preparation method and application of gel medicine sustained release preparation
  • Gel medicine sustained release preparation based on hydrophobically modified gemcitabine derivative as well as preparation method and application of gel medicine sustained release preparation
  • Gel medicine sustained release preparation based on hydrophobically modified gemcitabine derivative as well as preparation method and application of gel medicine sustained release preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Add dihydroxypolyethylene glycol (PEG1500) into a 250 mL three-necked flask, and remove water under vacuum at 120° C. for 3 hours. Cool to 80°C with argon, add lactide (LA), glycolide (GA) and stannous octoate (containing a small amount of toluene), and vacuum at 120°C for 30 minutes. Argon was blown, and the temperature was raised to 150° C. to react for 12 hours. After the reaction was completed, vacuum filtration was performed for 2 hours to remove unreacted monomers and low-boiling products in the system. The product was poured into deionized water at 80°C while it was hot, washed three times repeatedly, and freeze-dried to obtain the BAB type triblock polymer PLGA-PEG-PLGA with a yield of about 81%. The number-average and weight-average molecular weight (M n ,M w ) are 5280 and 6340 respectively, molecular weight distribution coefficient (M n / M w , ) is 1.20, and its polymer water system does not have heat-induced gelation performance.

Embodiment 2

[0057] Add dihydroxypolyethylene glycol (PEG1000) into a 250 mL three-necked flask, and remove water under vacuum at 120° C. for 3 hours. Cool to 80°C with argon, add lactide (LA), glycolide (GA) and stannous octoate (containing a small amount of toluene), and vacuum at 120°C for 30 minutes. Argon was blown, and the temperature was raised to 150° C. to react for 12 hours. After the reaction was completed, vacuum filtration was performed for 2 hours to remove unreacted monomers and low-boiling products in the system. The product was poured into deionized water at 80°C while it was hot, washed three times repeatedly, and freeze-dried to obtain the BAB type triblock polymer PLGA-PEG-PLGA with a yield of about 87%. The number-average and weight-average molecular weight (M n ,M w ) are 5210 and 6760 respectively, molecular weight distribution coefficient (M n / M w , ) is 1.30, and its polymer water system does not have heat-induced gelation performance.

Embodiment 3

[0059] Add monomethoxypolyethylene glycol (mPEG550) into a 250 mL three-necked flask, and remove water under vacuum at 120° C. for 3 hours. Cool to 80°C with argon, add lactide, glycolide and stannous octoate (containing a small amount of toluene), and vacuum at 120°C for 30 minutes. Argon was blown, and the temperature was raised to 150° C. to react for 12 hours. After the reaction, the initial product was dissolved in dichloromethane solution, precipitated with ether, and vacuum-dried for 48 hours to obtain the AB-type diblock polymer mPEG-PLGA with a yield of about 80%. By gel permeation chromatography (GPC, polystyrene is a standard sample), the number average and weight average molecular weight (M n ,M w ) are 4680 and 6100 respectively, molecular weight distribution coefficient (M n / M w , ) is 1.30, and its polymer water system does not have heat-induced gelation performance.

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Abstract

The invention relates to the technical field of medicine preparation, and specifically relates to a gel medicine sustained release preparation based on a hydrophobically modified gemcitabine derivative and application of the gel medicine sustained release preparation to preparation of antitumor drugs. The gel medicine sustained release preparation disclosed by the invention is mainly composed of agel carrier material, an effective amount of a hydrophobically modified gemcitabine derivative, and a solvent; gemcitabine molecules are modified with long fatty acid chains, and entrapment is conducted by using a PEG / polyester block copolymer thermally induced gel carrier, and thus slow release of the medicine, namely the hydrophobically modified gemcitabine derivative, in the gel carrier is realized by utilizing hydrophobic interaction between the medicine and the polymer carrier, so that a drug utilization rate is improved, long-term chemotherapy effects can be achieved, and meanwhile, thegel medicine sustained release preparation is capable of realizing the purposes of continuous chemotherapy and multiple radiotherapy sensitization after one time of injection when being used in combination with radiation therapy. Therefore, the gel medicine sustained release preparation disclosed by the invention is suitable for promotion and application.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a long-acting radiotherapy-sensitized gel sustained-release preparation based on a hydrophobically modified gemcitabine prodrug, a preparation method and application thereof. Background technique [0002] Cancer can be said to be the number one disease in the world, endangering the life and health of people in all countries. Clinical cancer treatment methods are still mainly surgical resection, chemotherapy and radiotherapy. However, it has been clinically proven that single chemotherapy or radiotherapy often cannot achieve the best curative effect, but has relatively large toxic and side effects. The search for efficient combination therapy has become a current research hotspot, because combination therapy can not only improve the curative effect, but also reduce the dose of drugs or radiation, and reduce side effects. [0003] Gemcitabine is a deoxycyt...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K31/7068A61K47/54A61K47/34A61P35/00
CPCA61K31/7068A61K47/542A61K9/06A61K47/34A61K9/0024A61P35/00
Inventor 俞麟杨孝伟丁建东
Owner FUDAN UNIV
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