Nanometer assembly based on immune checkpoint inhibitor and preparation method and application of nanometer assembly

A nano-assembly and methyl technology, applied in the field of medicine, can solve the problems of low treatment response rate, achieve good biocompatibility, enhance immune response, and relieve tumor immunosuppressive environment effects

Active Publication Date: 2019-07-30
SHANDONG UNIV
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as far as the inventors of this disclosure know, there are still many limitations in the current clinical application of monoclonal antibodies targeting the PD-1 / PD-L1 pathway, and the biggest obstacle is the low treatment response rate (only 20%)

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
  • Nanometer assembly based on immune checkpoint inhibitor and preparation method and application of nanometer assembly
  • Nanometer assembly based on immune checkpoint inhibitor and preparation method and application of nanometer assembly
  • Nanometer assembly based on immune checkpoint inhibitor and preparation method and application of nanometer assembly

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1: PLL-1-mt molecular synthesis.

[0056] 1) Boc protection of 1-methyl-D-tryptophan amino group (Boc-1-mt): use an analytical balance to accurately weigh 1-methyl-D-tryptophan, NaHCO 3 and di(tert-butyl)dicarbonate were dissolved in a mixed solution of water and tetrahydrofuran at a volume ratio of 1:1, and the mixture was stirred at 0°C for 10 minutes, and then kept at room temperature for 24 hours. After the reaction, the THF was spin-dried, and the aqueous layer was acidified to pH 1.0 with 1M HCl, and then extracted with ethyl acetate. Evaporation of ethyl acetate gave a milky white solid which was the target product Boc-1-mt.

[0057] (2) Synthesis of Boc-1-mt active intermediate ester (Boc-1-mt-NHS ester1): a certain amount of N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl) carbon Diimine hydrochloride was dissolved in anhydrous DMF, and Boc-1-mt was added. The reaction mixture was stirred at room temperature for 4 hours and used without furth...

Embodiment 2

[0060] Embodiment 2: proton nuclear magnetic resonance spectrum ( 1 H-NMR) to identify the molecular chemical structure of PLL-1-mt.

[0061] Weigh about 5 mg of PLL-1-mt prodrug and heavy water (D 2 O) dissolved and placed in a nuclear magnetic tube, using 400MHz proton nuclear magnetic resonance spectrum to measure its hydrogen nuclear magnetic resonance spectrum, using tetramethylsilane as an internal standard, and recording the chemical shift value (ppm) of the compound. The result is as figure 1 As shown, the NMR results can confirm that the characteristic peaks of PLL and 1-mt appear simultaneously in the newly synthesized molecule. pass 1 H-NMR spectrum can confirm the successful synthesis of PLL-1-mt molecule. Through the nuclear magnetic analysis of the PLL, it is obtained that m+n is 44, and through the ultraviolet spectrum analysis, it is obtained that m is 4 and n is 40.

Embodiment 3

[0062] Example 3: Preparation of aPD-L1@HC / PM nano vein preparation.

[0063] Accurately weigh 2 mg of HA-Ce6 molecule, dissolve it in 1.5 mL of water, and precisely weigh 0.5 mg of PLL-1-mt molecule, and dissolve it in 0.5 mL of water. Under ultrasonic conditions, the PLL-1-mt aqueous solution was added dropwise to the HA-Ce6 aqueous solution, and after reacting for 30 minutes, the nanocomposite (HC / PM ), and then post-adsorption of aPD-L1 monoclonal antibody. Disperse aPD-L1 in 10 μL PBS, then slowly drop it into the HC / PM nanocomposite solution using a stirrer under ice bath, and let stand for 10 minutes to obtain aPD-L1@HC / PM nanocomposite. Among them, HA-Ce6 references W.J.Li, C.F.Zheng, Z.Y.Pan, C.Chen, D.H.Hu, G.H.Gao, S.D.Kang, H.D.Cui, P.Gong, L.T.Cai, Smarthyaluronidase-activedtheranostic micelles for dual-modal imaging guided photodynamic therapy .Biomaterials 2016,10,10-19. Preparation.

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 discloses nanometer assembly based on an immune checkpoint inhibitor and a preparation method and application of the nanometer assembly. The nanometer assembly comprises a polymer, hyaluronic acid grafted with chlorin and a PD-L1 monoclonal antibody, wherein the structural formula of the polymer is shown in the description, the number-average molar mass of the polymer is 2000-6000, and the ratio of m to n is 1:(8-15). The nanometer assembly can achieve integrated combination treatment of enhancing the enhance antigen presentation stage and the lymphocyte activation, proliferationand differentiation stage and the tumor removal stage.

Description

technical field [0001] The present disclosure relates to the field of medical technology, in particular to nano-assemblies based on immune checkpoint inhibitors and their preparation methods and applications. Background technique [0002] The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art. [0003] According to reports, among cancer-related deaths, about 90% of cancer patients die from malignant tumor metastasis. Malignant melanoma is a type of malignant tumor derived from melanocytes, which is commonly found in the skin, mucous membrane, eye choroid and other parts. Melanoma is the most malignant type of skin tumor, and it is very prone to distant metastasis. Currently, classic cancer treatments, such as surgical resection, chemotherapy, and radiotherapy, all have very limited efficacy in treating advanced melanoma metastases. With the in-depth study of tumor immunology, immunotherapy...

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 Applications(China)
IPC IPC(8): C08G69/48C08G69/10A61K39/395A61K41/00A61K9/51A61K47/34A61K47/36A61P35/00A61P35/02
CPCA61K9/5146A61K9/5161A61K39/39558A61K41/0052A61K2039/876A61P35/00A61P35/02C08G69/10C08G69/48A61K2300/00
Inventor 栾玉霞李倩
Owner SHANDONG 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