Preparation method of 5-fluorouracil molecular surface imprinting microsphere

A technology of fluorouracil and surface imprinting, which can be applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulations, etc., and can solve the problems such as the destruction of imprinted holes, the cumbersome preparation process, and the weak pH sensitivity. , to achieve the effect of reducing side effects and simple preparation process

Inactive Publication Date: 2015-03-11
ZHONGBEI UNIV
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The currently reported 5-fluorouracil oral colon-targeted drug release system prepared by molecular imprinting technology is mainly prepared by traditional bulk polymerization method. The preparation process of this method is cumbersome. Strong, the cumulative release rate of the drug in the simulated small intestinal fluid has exceeded 30% [Francesco Puoci , Francesca Iemma , Giuseppe Cirillo , Nevio Picci , Pietro Matricardi and Franco Alhaique . Molecules 2007, 12:805], or the release time does not exceed 6 hours [Baljit Singh, Nirmala Chauhan. Acta Biomaterialia, 2008(4): 1244]

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] In a four-neck flask, dissolve 5.6g of sodium p-styrenesulfonate in 40mL of pure water with pH=1, then add 1.75g ​​of 5-fluorouracil, and stir for 5h. After adding 0.4 g of cross-linked polyvinyl alcohol microspheres (CPVA) to swell overnight, 0.598 g of cross-linking agent N,N'-methylenebisacrylamide (MBA) was added. Nitrogen was purged for 30 minutes to exclude air. Add 0.364 mL of catalyst concentrated sulfuric acid to 10 mL of pure water with pH=1 dissolved in 0.2 g of initiator ammonium cerium sulfate, and add it to the above-mentioned four-neck flask. Under the condition of nitrogen protection, the temperature was raised to 35° C. for 6 hours. Obtain 5-fluorouracil molecular surface imprinted microspheres. Then use 2g / L NaHCO 3 The template was eluted with the solution until 5-fluorouracil could not be detected by ultraviolet light, and then washed repeatedly with distilled water to neutrality, and dried in vacuum to constant weight to obtain 5-fluorouracil ...

Embodiment 2

[0016] In a four-necked flask, dissolve 5.6g of sodium p-styrene sulfonate in 40mL of ultrapure water with pH=1, then add 2.65g of 5-fluorouracil, and stir for 5h. After adding 0.3 g of cross-linked polyvinyl alcohol microspheres (CPVA) to swell overnight, 1.386 g of cross-linking agent N,N'-methylenebisacrylamide (MBA) was added. Nitrogen was purged for 30 minutes to exclude air. Add 0.6 mL of catalyst concentrated sulfuric acid to 10 mL of pH=1 ultrapure water dissolved with 0.3 g of initiator ammonium cerium sulfate, and add it to the above-mentioned four-neck flask. Under the condition of nitrogen protection, the temperature was raised to 45° C. for 8 hours. Obtain 5-fluorouracil molecular surface imprinted microspheres. Then use 1.5g / L Na 2 CO 3 The template was eluted with the solution until 5-fluorouracil could not be detected by ultraviolet light, and then washed repeatedly with distilled water to neutrality, and dried in vacuum to constant weight to obtain 5-fluor...

Embodiment 3

[0018] In a four-necked flask, dissolve 5.6g of sodium p-styrenesulfonate in 40mL of ultrapure water with pH=1, then add 2g of 5-fluorouracil, and stir for 5h. Then add 0.5 g of cross-linked polyvinyl alcohol microspheres (CPVA) to swell overnight, then add 0.992 g of cross-linking agent N,N' - Methylenebisacrylamide (MBA). Nitrogen was purged for 30 minutes to exclude air. Add 0.45 mL of catalyst concentrated sulfuric acid into 10 mL of ultrapure water with pH=1 dissolved in 0.25 g of initiator cerium ammonium sulfate, and add it into the above-mentioned four-neck flask. N 2 Under protective conditions, the temperature was raised to 45° C. for 7 hours. Obtain 5-fluorouracil molecular surface imprinted microspheres. The template was then eluted with 1g / L NaOH solution until 5-fluorouracil could not be detected by ultraviolet light, then washed repeatedly with distilled water until neutral, dried in vacuum to constant weight to obtain 5-fluorouracil molecular surface imprin...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the technical field of colorectal carcinoma positioned-release treatment medicines and high-molecular materials, and concretely relates to a preparation method of 5-fluorouracil molecular surface imprinting microsphere having pH sensitivity and time-delay characteristic. The method comprises the following steps: 1) dissolving p-styrene sodium sulphonate in purified water, adding 5-fluorouracil, and stirring to obtain a prepolymer; wherein a functional monomer p-styrene sodium sulphonate (SSS) and a template molecule 5-FU from a non-covalent bond through electrostatic interaction, and 2) adding vinyl alcohol microsphere in the prepolymer, adding a cross-linking agent N, N'-methylene bisacrylamide, introducing nitrogen to remove air, adding an initiator and a catalyst, and reacting under the nitrogen protection condition to obtain the 5-fluorouracil molecular surface imprinting microsphere. The prepared imprinting microsphere drug loaded MIP-PSSS / CPVA microsphere has pH sensitivity, and the release amount is increased by increasing of the pH value.

Description

technical field [0001] The invention belongs to the technical field of colon cancer localized release therapeutic drugs and polymer materials, and specifically relates to a method for preparing 5-fluorouracil molecular surface imprinted microspheres with pH sensitivity and time lag. Background technique [0002] Colorectal cancer is currently the third most common cancer in the world, with an annual death toll of 655,000. 5-Fluorouracil (5-FU) is the drug of choice for the treatment of colon cancer. But at the same time, it has the disadvantages of fast metabolism in vivo, short half-life (10-20min), low bioavailability, high toxicity to normal cells, and poor selectivity to tumor cells. Moreover, the concentration in the colon reached by intravenous injection is low, and patient compliance is poor. Can cause severe gastrointestinal reactions and bone marrow poisoning and other side effects. In order to overcome the above shortcomings of 5-FU and improve the treatment e...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K31/513A61K47/32A61P35/00A61P1/00
Inventor 门吉英高保娇王蕊欣么兰杜俊玫
Owner ZHONGBEI UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap