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

Preparation method of crosslinked nanodrug based on active reaction type one-step method

A nano-drug and reactive technology, which is applied in the direction of drug combination, pharmaceutical formula, medical preparations of non-active ingredients, etc., can solve the problems of non-crosslinking of chemically bonded nano-drugs, complex and multi-step preparation of chemically-bonded nano-drugs, etc. Achieve the effects of ultra-high stability, increased maximum tolerance, and stable cross-linked structure

Active Publication Date: 2017-08-29
SUZHOU UNIV
View PDF3 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a preparation method of cross-linked nano-medicine based on the active reaction type one-step method (referred to as the reaction-loading method), and the nano-medicine with stable drug bonding and circulation stability can be obtained through simple preparation, which solves the problem of In the prior art, the preparation of chemically bonded nano-medicines is complex, requiring catalysts and multi-step preparation; and the product prepared by the present invention has a stable cross-linked structure, which avoids the problem of non-cross-linking of existing chemically-bonded nano-medicines

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
  • Preparation method of crosslinked nanodrug based on active reaction type one-step method
  • Preparation method of crosslinked nanodrug based on active reaction type one-step method
  • Preparation method of crosslinked nanodrug based on active reaction type one-step method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] cRGD-PS-DM1 cross-linked nanomedicine was directly formed by co-polymer PEG-P(TMC-DTC) and cRGD-PEG-P(TMC-DTC) (w / w80 / 20) encapsulating DM1 while self-assembling. The invention creatively realizes sulfur-sulfur-sulfhydryl exchange reaction and sulfur-sulfur crosslinking at the same time.

[0043] The overall reaction idea of ​​this embodiment is:

[0044]

[0045] Under nitrogen protection, NHS-PEG-OH ( M n = 7.5 kg / mol, 75 mg, 10 μmol), TMC (200 mg, 1.6 mmol) and DTC (50 mg, 0.26 mmol) were dissolved in 1.1 mL of anhydrous dichloromethane, followed by adding diphenyl phosphate (DPP, 25 mg, 100 μmol) in a closed reactor at 30 °C for 72 h, terminated, precipitated twice in glacial ether, filtered and vacuum dried overnight to obtain NHS-PEG-P (TMC-DTC). Yield: 84.6%. 1 H NMR (600 MHz, CDCl 3 ): PEG: δ3.64; TMC: δ 2.06, 4.24; DTC: δ 3.02, 4.19; NHS: δ 2.52. M n ( 1 H NMR) =31.8 kg / mol. M n (GPC) = 34.8 kg / mol, M w / M n = 1.14; then the obtained copo...

Embodiment 2

[0065] According to Example 1, the polymers PEG-P (TMC-DTC) and MAL-PEG-P (TMC-DTC) were prepared, and the targeting molecule Anti-CD19-PEG of the anti-CD19 antibody was prepared from the latter -P(TMC-DTC), the chemical structure is as follows:

[0066]

[0067] Further preparation of cross-linked nano-drugs and targeted cross-linked nano-drugs, which are vesicle structures with a particle size of about 90-100 nm; loaded with maytansine DM1, the drug loading DLC ​​can reach 10-15wt.%; MTD research results show The MTD values ​​of cross-linked vesicle nanomedicine and targeted cross-linked vesicle nanomedicine are nearly 4 times higher than that of free DM1; the tumor inhibition rate (TIR ) respectively exceeded 60% and 90%; the median survival of mice exceeded 35 days and 60 days (PBS was 25 days), and the toxic and side effects on the main organs of mice were very small.

Embodiment 3

[0069] According to Example 1, TMC was replaced with LA to prepare polymers PEG-P (LA-DTC) and NHS-PEG-P (LA-DTC), and the targeting molecule was prepared from the latter to target polymerization of EGFR targeting polypeptide GE11 Material GE11-PEG-P (LA-DTC), the chemical structure is as follows:

[0070]

[0071] Further preparation of cross-linked nano-drugs and targeted cross-linked nano-drugs, which are vesicle structures with a particle size of about 50-70 nm; loaded with the drug 6-mercaptopurine (6MP) with its own mercapto group, and the drug loading DLC ​​is 5- 10 wt.%; MTD results showed that the MTD value of cross-linked vesicle nano-drugs and targeted cross-linked vesicle nano-drugs was 6 times that of free 6MP; The tumor inhibition rate (TIR) ​​of triple-negative breast cancer MDA-MB-231 subcutaneous tumors exceeded 60% and 85% respectively; the median survival of mice exceeded 47 days and 58 days (PBS was 30 days), and the main effect on mice Visceral almost ...

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 discloses a preparation method of a crosslinked nanodrug based on an active reaction type one-step method. The preparation method specifically comprises the following step: adding a polymer and a drug with sulfydryl into a solution to be mixed to dialyze to obtain a crosslinked nanodrug, wherein the side chain of the polymer contains a dithiolane structure. The circularly stable nanodrug can be obtained by simple preparation, so that the defects that in the prior art, a chemically bonded nanodrug is complex to prepare and needs a catalyst and the like are overcome. The product prepared by the invention has a stable crosslinking structure and avoids the problem that an existing chemically bonded nanodrug is not crosslinked; and on a B16F10 melanoma-loading model, the nanodrug shows a good curative effect, and the tumor inhibition rate exceeds 90%. The active targeted crosslinked nanodrug has a huge potential application in the field of cancer chemotherapy.

Description

technical field [0001] The invention belongs to the technical field of polymer nano-medicines, and in particular relates to a preparation method of a cross-linked stable nano-medicine based on an active-response one-step method, and the circulation-stable nano-medicine can be obtained through simple preparation. Background technique [0002] Chemotherapy is the most common means of treating malignant tumors. In the past few decades, in order to improve the selectivity of chemotherapy drugs and reduce the side effects, researchers have explored various polymer nanocarriers. Generally speaking, there are two ways to encapsulate drugs in polymer nanocarriers, one is physical embedding, and the other is to form polymer-drug conjugates through chemical bonds. For example, NK105 and Genexol-PM are two typical examples of using micelles to encapsulate paclitaxel (PTX), while NK911 is a model of chemically bonded nano-drugs. Physically embedded nanomedicines are more prone to prob...

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): A61K47/69A61K47/68A61K47/64A61K47/54A61K47/61A61K31/537A61P35/00
CPCA61K31/537
Inventor 钟志远孟凤华孟浩张玥
Owner SUZHOU UNIV
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