Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of an ionizable lipid compound in nucleic acid drug delivery system

A nucleic acid drug and delivery system technology, applied in drug delivery, nano-drugs, medical preparations of non-active ingredients, etc., can solve the problems of increased drug dose, increased liver metabolic burden, and low delivery efficiency of the delivery system, reducing the The effect of cumulative side effects

Active Publication Date: 2022-08-02
WUHAN BINHUI BIOTECH CO LTD
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of the existing nucleic acid drug carriers are easy to accumulate in the liver after entering the body, increasing the metabolic burden of the liver and causing obvious toxic and side effects
Or there is a phenomenon that due to the low delivery efficiency of the delivery system, it is easy to increase the dosage of the drug and cause toxic side effects

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 an ionizable lipid compound in nucleic acid drug delivery system
  • Application of an ionizable lipid compound in nucleic acid drug delivery system
  • Application of an ionizable lipid compound in nucleic acid drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Synthetic route of compound 1:

[0093]

[0094] Step 1: Synthesis of Compound 1-1:

[0095] Add linolenic alcohol (0.267 g, 1 mmol) and triethylamine (0.133 g, 1.3 mmol) to the ice-water bath in the reaction flask, add dichloromethane (6 mL), and dissolve acryloyl chloride (0.11 g, 1.2 mmol) in dichloromethane (2.2 mL), slowly dropped into the reaction flask, the reaction continued for 10 minutes, the reaction was kept below 10° C., and finally the ice bath was removed, and the reaction solution was reacted at room temperature for 2 hours. Washed with saturated brine to obtain crude product, which was purified by chromatography (silica gel column, eluent is petroleum ether containing 0.5% EA (volume percent)), and the pure product was evaporated to obtain compound 1 as light yellow oil -1(2-Allenic acid (9Z, 12Z)-octadecadienyl ester) (0.173 g, yield: 50%) The hydrogen spectrum of compound 1-1 is shown in figure 1 .

[0096] 1H NMR (400MHz, CDCl 3 )δ: 6.41 (dd, ...

Embodiment 2

[0101] Synthetic route of compound 2

[0102]

[0103] Step 1: Synthesis of Compound 2-1

[0104]6-Bromohexanoic acid (1.0 g, 5.13 mmol) and undecanol (1.77 g, 10.25 mmol) were dissolved in dichloromethane (60 mL) and 1-(3-dimethylaminopropyl)-3-ethyl was added carbodiimide hydrochloride (EDC hydrochloride, 0.98 g, 5.13 mmol) and DMAP (0.125 g, 1.03 mmol). The mixture was stirred at normal temperature for 18 hours. After the reaction was over, it was diluted with DCM (200 mL) and saturated with NaHCO 3 (100 mL) and brine (100 mL). Combine the organic layers with anhydrous Na 2 SO 4 Drying and removal of solvent in vacuo gave crude product, which was purified by chromatography (silica gel column, eluent: petroleum ether containing 0.5% EA (v / v)) and evaporated to give compound 2 as a pale yellow oil -1(undecyl 6-bromohexanoate) (0.69 g, 38.6% yield). For the hydrogen spectrum of compound 2-1, see Figure 5 .

[0105] 1H NMR (400MHz, CDCl 3 )δ: 4.10(t, J=6.6Hz, 2H),...

Embodiment 3

[0110] Synthetic route of compound 3

[0111]

[0112] Step 1: Synthesis of Compound 3-1

[0113] 8-Bromooctanoic acid (1.139 g, 5.13 mmol) and 3,7-dimethyloct-6-en-1-ol (citronellol, 1.599 g, 10.25 mmol) were dissolved in dichloromethane (60 mL), fully After dissolution, EDC hydrochloride (0.98 g, 5.13 mmol) and DMAP (0.125 g, 1.03 mmol) were added. The mixture was stirred at normal temperature for 18 hours. After the reaction was over, it was diluted with DCM (200 mL) and saturated with NaHCO 3 (100 mL) and brine (100 mL). Combine the organic layers with anhydrous Na 2 SO 4 Dry, remove the solvent in vacuo to give the crude product, which is purified by chromatography (silica gel column, eluent is petroleum ether containing 0.5% EA (v / v)) and evaporated to give compound 3 as a pale yellow oil -1(3,7-dimethyloct-6-enyl 6-bromohexanoate) (0.648g, 35%) See the hydrogen spectrum of compound 3-1 Figure 8 .

[0114] 1H NMR (400MHz, CDCl 3 )δ: 5.09(s, 1H), 4.18-4.01(m,...

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
sizeaaaaaaaaaa
sizeaaaaaaaaaa
particle sizeaaaaaaaaaa
Login to View More

Abstract

The present invention provides an application of an ionizable lipid compound in a nucleic acid drug delivery system. Most of the existing nucleic acid drug carriers have problems such as low delivery efficiency in vivo or accumulation of toxic and side effects in the liver. In order to solve these problems, the present invention provides a new drug delivery system. The nucleic acid drug delivery system of the present invention is suitable for a variety of administration modes, has little liver toxicity and high nucleic acid delivery efficiency, and can even efficiently deliver nucleic acid drug molecules to the spleen with high specificity and efficiently translate them into target molecules.

Description

technical field [0001] The invention belongs to the technical field of nucleic acid drug delivery, in particular to the application of an ionizable lipid compound in a nucleic acid drug delivery system. Background technique [0002] The active molecules of nucleic acid drugs include messenger RNA (mRNA), small interfering RNA (siRNA), antisense oligonucleotide (ASO) or plasmid DNA (pDNA), which have great potential for application in vaccines and gene therapy in vitro or in vivo . How to successfully deliver nucleic acid drug molecules to in vivo cells and express them efficiently to achieve the purpose of prevention or treatment is one of the urgently needed technologies. Most of the existing nucleic acid drug carriers are prone to accumulate in the liver after entering the body, increase the metabolic burden of the liver, and cause obvious toxic and side effects. In addition, there is a phenomenon that the delivery system is not very efficient, and it is easy to increase...

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): A61K47/18
CPCA61K47/18A61K48/0033A61K31/7105A61K31/715A61K9/5123A61K9/0019B82Y5/00
Inventor 崔艳芳吉帅洁张宝倩刘滨磊
Owner WUHAN BINHUI BIOTECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com