A drug-loaded nanofiber microsphere/hydrogel composite and its preparation method and application

A drug-loaded nanometer and hydrogel technology, which is applied in drug combination, drug delivery, and pharmaceutical formulations, can solve the problems of small hydrophobicity of PPO chain segments, high critical micelle concentration, and increased raw material usage, so as to solve the problem of migration Positioning and disintegration, good biosafety, and the effect of reducing the number of administrations

Active Publication Date: 2018-12-21
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the high critical gel concentration of poloxamer polymers, for example, trans-poloxamer 10R5 cannot form a gel even when the concentration is greater than 90%, so this material is used to prepare gels. Glue will undoubtedly greatly increase the amount of raw materials used, which will greatly increase the cost of preparation
In addition, due to the low hydrophobicity of the PPO chain segment, poloxamers usually have a high critical micelle concentration, which also makes them vulnerable to damage after injection into the human body
Therefore, it is difficult to form a composite drug delivery system with microspheres in the form of hydrogels using pure poloxamer materials.

Method used

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  • A drug-loaded nanofiber microsphere/hydrogel composite and its preparation method and application
  • A drug-loaded nanofiber microsphere/hydrogel composite and its preparation method and application
  • A drug-loaded nanofiber microsphere/hydrogel composite and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0059] Under the protection of nitrogen flow, L-lactide, poloxamer F68 with a mass ratio of 2.57 and 0.3 wt% stannous octoate based on the total mass of L-lactide and poloxamer were heated to 180 °C and stirred React for 24 hours, cool to room temperature, then add dichloromethane to dissolve the reaction product, then put it into methanol 10 times the volume of dichloromethane to precipitate, filter, dissolve the white precipitate with dichloromethane and put it in dichloromethane Continue to precipitate, filter, and dry in diethyl ether of 10 times the volume of methyl chloride to obtain the theoretical molecular weight Mn a 3.0×10 4 Polylactic acid-poloxamer F68-polylactic acid multi-block polymer. Mn calculated by NMR b 2.85×10 4 , GPC results measured Mw c 4.23×10 4 , Mn c 3.02×10 4 .

Embodiment 2

[0061] Under the protection of nitrogen flow, L-lactide with a mass ratio of 0.786, poloxamer F68 and 0.3wt% stannous octoate based on the total mass of L-lactide and poloxamer were heated to 150°C and stirred React for 15 hours, cool to room temperature, then add dichloromethane to dissolve the reaction product, then put it into methanol 10 times the volume of dichloromethane to precipitate, filter, dissolve the white precipitate with dichloromethane and put it in dichloromethane Continue to precipitate, filter, and dry in diethyl ether of 10 times the volume of methyl chloride to obtain the theoretical molecular weight Mn a 1.5×10 4 Polylactic acid-poloxamer F68-polylactic acid multi-block polymer. Mn calculated by NMR b1.36×10 4 , GPC results measured Mw c 2.30×10 4 , Mn c 1.52×10 4 .

Embodiment 3

[0063] According to the above synthesis route, under the protection of nitrogen flow, L-lactide, poloxamer F68 with a mass ratio of 1.38 and 0.3wt% stannous octoate based on the total mass of poloxamer and L-lactide Heat to 140°C and stir for 20 hours, cool to room temperature, then add dichloromethane to dissolve the reaction product, then put it into methanol 10 times the volume of dichloromethane to precipitate, filter, and dissolve the white precipitate with dichloromethane After that, put it into diethyl ether of 10 times the volume of dichloromethane and continue to precipitate, filter, and dry to obtain the theoretical molecular weight Mn a 2.5×10 4 Polylactic acid-poloxamer F68-polylactic acid multi-block polymer. Mn calculated by NMR b 2.56×10 4 , GPC results measured Mw c is 3.74×10 4 , Mn c 2.38×10 4 .

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Abstract

The invention discloses a drug-loaded nanofiber microsphere / hydrogel compound and a preparation method and application thereof. According to the compound, firstly, polylactic acid-poloxamer F68-polylactic acid multi-block polymer and microtubule inhibition type drugs are made into drug-loaded nanofiber microspheres through a low temperature freezing / phase separation method, and then the drug-loaded nanofiber microspheres are dispersed into hydrogel formed through configuration of the polylactic acid-poloxamer F68-polylactic acid multi-block polymer. The content of the drug-loaded nanofiber microspheres in the compound is 5-35 wt%, the particle size is 20-200 microns, the actual drug loading amount is 7.45-17.32%, and the encapsulation efficiency is 86.64-93.17%; the content of the polylactic acid-poloxamer F68-polylactic acid multi-block polymer in sol is 10 wt% at a minimum, and the sensitivity temperature of the polylactic acid-poloxamer F68-polylactic acid multi-block polymer is greater than or equal to 25 DEG C. By means of the drug-loaded nanofiber microsphere / hydrogel compound and the preparation method and application thereof, the drug amount of the injured part can be increased, acting time is prolonged, the number of drug administration times is remarkably reduced, and the problems of displacement and disintegration of the microspheres at the implantation position can be effectively solved.

Description

technical field [0001] The invention belongs to the technical field of medical polymer materials and their preparation and application, and in particular relates to a drug-loaded nanofiber microsphere / hydrogel composite and its preparation method and application. Background technique [0002] Spinal cord injury has the characteristics of high disability rate, low case fatality rate, and heavy social burden. It is one of the worldwide problems that the medical field urgently needs to solve. According to incomplete statistics, 250,000 people in the United States are affected by spinal cord injuries. Not only that, there are 13,400 new cases of spinal cord injuries every year. Spinal cord injury can be divided into two processes: primary injury and secondary injury. In the process of primary injury, the integrity of the cell membrane will be destroyed due to injury factors, such as spinal fracture, flexion, rotation, dislocation, compression, etc., resulting in a large amount ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/06A61K9/00A61K47/34A61K9/16A61P25/28
CPCA61K9/0019A61K9/06A61K9/1641A61K31/337A61K47/34
Inventor 郭刚周良学陈海锋高祥魏于全
Owner SICHUAN UNIV
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