Chemotherapy-immunotherapy combined drug and preparation method and application thereof

A technology for chemo-immunity and chemotherapeutic drugs, applied in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve the problems of low level of tumor-infiltrating lymphocytes, low mutation rate of TNBC tumor cells, weak immune microenvironment, etc. Metastasis, inhibitory Treg reduction, growth inhibitory effects

Pending Publication Date: 2021-09-07
SUZHOU UNIV
View PDF4 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, single immunotherapy such as PD-1/PD-L1 monoclonal antibody is only effective for 20%-25% of patients, and the objective response rate (ORR) for di...

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
  • Chemotherapy-immunotherapy combined drug and preparation method and application thereof
  • Chemotherapy-immunotherapy combined drug and preparation method and application thereof
  • Chemotherapy-immunotherapy combined drug and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example

[0040] The synthesis of PEG-P(CL-DTC) block copolymer is based on MeO-PEG-OH ( M n = 2.0 kg / mol) is obtained by ring-opening polymerization of DTC and CL initiated by a macromolecular initiator and diphenyl phosphate (DPP) as a catalyst. Specifically, in an inert gas glove box, MeO-PEG-OH (800 mg, 0.4 mmol), DPP (1.0 g, 4 mmol), DTC (400 mg, 2.1 mmol), CL (400 mg, 3.5 mmol) and anhydrous DCM (3.2 mL), stirred and dissolved, sealed, removed from the glove box, and placed in a 40 ºC oil bath with magnetic stirring for 48 h. After the reaction was completed, glacial acetic acid was added to terminate the reaction, precipitated twice in 30 times the volume of glacial ether, filtered by suction, and dried in vacuum for 24 h to obtain PEG 2k -P(CL 1k -DTC 1k ), the preparation route is as follows:

[0041]

[0042] Using MeO-PEG-OH with a molecular weight of 5000 Da as the initiator and DPP as the catalyst, controllable ring-opening polymerization of CL and DTC according to ...

Embodiment 1

[0050] Example 1 Chemotherapy-immune combination drug

[0051] Preparation of PTX micelles

[0052] Combine PTX and PEG 2k -P(CL 1k -DTC 1k ) were dissolved in PEG 350 according to different mass ratios (5 / 100, 10 / 100, 20 / 100, 30 / 100), and the polymer concentration was 50 mg / mL. After conventional ultrasonication for 5 min, 100 mL of the mixture was poured into the bottom of 900 mL of PB solution (pH 7.4, 10 mM) at 37 °C, and stood without stirring during the process. After injecting, use a pipette gun to stick to the liquid surface and pipette 5 times to obtain a PTX drug loading of 4.8 wt. %~23.1 wt. % micellar MS-PTX, which is a non-targeting small micellar nanomedicine. The particle size and particle size distribution (PDI) were determined by DLS, and the micelle morphology was determined by TEM. MS-PTX (polymer concentration: 0.1 mg / mL) was dissolved in acetonitrile containing 20 mM DTT, and then the PTX concentration was tested by HPLC, and the drug loading and dr...

Embodiment 2

[0066] The targeting micelles loaded with PTX are composed of amphiphilic block polymer PEG 2k -P(CL 1k -DTC 1k ) and the polymer Ta-PEG-P (CL-DTC) coupled with targeting molecules (Ta is the polypeptide cRGD, ATN1 or ATN2) are self-assembled in the aqueous phase. 2.5%, 5%, 7.5%, 10% or 20% of ATN1-PEG-P (CL-DTC), ATN2-PEG-P (CL -DTC) or cRGD-PEG-P (CL-DTC) as the initial polymer solution, then mixed with the PTX solution, all the other steps are the same as in Example 1, to obtain micelles ATN1-MS-PTX, ATN2 with different polypeptide surface densities -MS-PTX and cRGD-MS-PTX, for targeting small micellar nanomedicine.

[0067] After mixing PEG-(CL-DTC) and targeting polymers coupled with cRGD, PHSCNK or PhScNK in different proportions, targeting micelles were prepared, and the same method as in Example 1 was used to keep the PTX drug loading at 4.8 wt. %, three series of micellar cRGD-MS-PTX, ATN1-MS-PTX and ATN2-MS-PTX with different targeting molecule densities were pre...

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
Molecular weightaaaaaaaaaa
Login to view more

Abstract

The invention discloses a chemotherapy-immunotherapy combined drug and a preparation method and application thereof. A PTX micelle based on PEG-P (CL-DTC) is designed, and the technical effect of combination of the PTX micelle and vesicles (CPs-CDN) with asymmetric membrane structures of interferon-gene-carrying stimulating protein (STING) pathway agonist Cyclic Dinucleotide (CDN) in treatment of breast cancer (TNBC) is studied. The PTX micelle is simple in preparation method, small in particle size and high in drug loading capacity and has good stability and reduction responsiveness. Experiments show that after the PTX micelle is combined with the CPs-CDN, more BMDC maturation can be promoted, CD4<+> T and CD8<+> T cells in tumors and spleens are significantly increased, inhibitory Treg is reduced, tumor growth and lung metastasis are obviously inhibited, the lifetime of mice is prolonged, and the advantages of chemotherapy-immunotherapy are embodied.

Description

technical field [0001] The invention belongs to nano-medicine technology, and in particular relates to a chemotherapy-immunity combination medicine and a preparation method and application thereof. Background technique [0002] In the later stage of chemotherapy, many patients will have adverse prognostic reactions such as drug resistance, cancer cell metastasis, and tumor recurrence. For highly metastatic tumors, such as triple-negative breast cancer that does not express progesterone receptor, estrogen receptor, and human epidermal growth receptor (TNBC) patients are pretty much helpless. The recently emerging immunotherapy has shown great potential in tumor treatment, especially the immune checkpoint therapy based on PD-1 monoclonal antibody, PD-L1 monoclonal antibody, or CTLA-4 monoclonal antibody. Immunological monitoring to achieve tumor therapy. However, single immunotherapy such as PD-1 / PD-L1 monoclonal antibody is only effective for 20%-25% of patients, and the ob...

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): A61K9/107A61K47/10A61K9/127A61K47/64A61K31/7076A61P35/00A61P35/04A61P37/04A61K31/337
CPCA61K9/1075A61K47/10A61K31/337A61K9/1273A61K31/7076A61K47/64A61P35/00A61P37/04A61P35/04A61K2300/00
Inventor 孟凤华邱欣昀郭贝贝钟志远
Owner SUZHOU 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