Application of midazolam nanocrystal in preparation of drugs for improving blood-brain barrier permeability

A technology of midazolam and blood-brain barrier, applied in the field of medicine

Active Publication Date: 2021-03-02
ACADEMY OF MILITARY MEDICAL SCI
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nanosuspensions are neutral and less irritating, but because midazolam is a poorly soluble dr

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of midazolam nanocrystal in preparation of drugs for improving blood-brain barrier permeability
  • Application of midazolam nanocrystal in preparation of drugs for improving blood-brain barrier permeability
  • Application of midazolam nanocrystal in preparation of drugs for improving blood-brain barrier permeability

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0227] Example 1 Preparation of midazolam nanocrystal suspension

[0228] Add 2.5g of HPMC E5 into 100ml of water, heat to 50°C, stir until completely dissolved, then add 1g of SDS, 5g of midazolam, and homogenize by ultrasonication for 5min to fully wet the midazolam and suspend evenly. Pour the primary mixture into a wet mill with an initial rotation speed of 1500rpm, and increase the rotation speed by 500rpm every 5min until the rotation speed reaches 3000rpm, and continue grinding for 1h. The ground nano-suspension was diluted 200 times, and the particle size of the prepared nano-crystals was detected to be 286.6 nm, the polydispersity index (PDI) was 0.124, and the Zeta potential was -23.4 mV.

Embodiment 2

[0263] Example 2 Preparation of midazolam nanocrystal suspension

[0264] Add 2.5g of HPMC E5 to 100ml of water, heat to 55°C, stir until completely dissolved, then add 0.5g of SDS and 5g of midazolam, and homogenize by ultrasonication for 5min to fully wet the midazolam and suspend evenly. Pour the initial mixture into a wet mill, the initial speed is 1500rpm, and the speed is increased by 500rpm every 5 minutes until it reaches 3000rpm, and the grinding is continued for 1h to obtain the product. The ground nanosuspension was diluted 200 times, and the particle size of the prepared midazolam nanocrystals was detected to be 267.3 nm, the polydispersity index (PDI) was 0.132, and the Zeta potential was -28.1 mV.

Embodiment 3

[0341] Example 3 Preparation of midazolam nanocrystal suspension

[0342] Add 2.5g of HPMC E5 into 100ml of water, heat to 60°C, stir to dissolve, then add 0.5g of SDS and 10g of midazolam, and homogenize by ultrasonication for 5min to fully wet the midazolam and suspend evenly. Pour the initial mixture into a wet mill, the initial speed is 1500rpm, and the speed is increased by 500rpm every 5 minutes until it reaches 3500rpm, and the grinding is continued for 2h to obtain the product. The ground nanosuspension was diluted 200 times, the detected particle size was 223.6nm, the polydispersity index (PDI) was 0.124, and the Zeta potential was -25.8mV.

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

PropertyMeasurementUnit
Particle sizeaaaaaaaaaa
Particle sizeaaaaaaaaaa
Particle sizeaaaaaaaaaa
Login to view more

Abstract

The invention provides an application of a midazolam nanocrystal and a composition thereof in medicines for improving blood-brain barrier permeability. According to the midazolam nanocrystal, the solubility problem is solved, the bioavailability is improved, the problem that the treatment effect is poor when tablets and injection are used as anticonvulsant and antiepileptic drugs is solved, and the midazolam nanocrystal can effectively penetrate through a blood brain barrier and is used for treating epilepsy. In addition, the invention provides a technical platform, and the blood-brain barrierpermeability of the brain medicine is improved by the nanocrystalline preparation in the presence of a space protective agent and a charge stabilizer.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of midazolam nanocrystals in the preparation of medicines for improving blood-brain barrier permeability. Background technique [0002] Midazolam [8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-α][1,4]benzodiazepine, the structure is as follows Shown in Ⅰ] It acts through the γ-aminobutyric acid (GABA) receptor binding site, inhibits the reverse transport of glutamate carrier in human glial cells, and reduces the release of excitatory transmitter glutamate, thereby effectively controlling Convulsions. The indications for midazolam maleate tablets are "sleep disorders, insomnia, especially suitable for those who have trouble falling asleep, and premedication for surgery or diagnostic procedures". The indications for midazolam injection are "premedication before induction of anesthesia, induction and maintenance of anesthesia, conscious sedation ...

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
IPC IPC(8): A61K31/5517A61K45/06A61K9/10A61K47/10A61K47/44A61K47/38A61P25/08
CPCA61K31/5517A61K45/06A61K9/10A61K47/10A61K47/44A61K47/38A61P25/08A61K2300/00
Inventor 郑爱萍张洵李蒙张慧高静刘楠王增明高翔
Owner ACADEMY OF MILITARY MEDICAL SCI
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