Pegylated icd inducer-ido inhibitor nanoconjugate and its preparation method and application

A technology of PEGylation and polyethylene glycol, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc. It can solve cumbersome methods, poor therapeutic effects, and non-specific accumulation, etc. problem, achieve the effect of reducing non-specific accumulation and improving therapeutic index

Active Publication Date: 2021-06-01
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, after research by the inventors of the present invention, it has been found that, firstly, the method of co-delivery of OXA and 1-MT with two drugs is relatively cumbersome; nonspecific accumulation in the liver and spleen) and is less responsive to treatment

Method used

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  • Pegylated icd inducer-ido inhibitor nanoconjugate and its preparation method and application
  • Pegylated icd inducer-ido inhibitor nanoconjugate and its preparation method and application
  • Pegylated icd inducer-ido inhibitor nanoconjugate and its preparation method and application

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Embodiment approach

[0061] The third embodiment of the present invention provides a use of the above pegylated ICD inducer-IDO inhibitor conjugate in the preparation of tumor therapeutic drugs.

[0062] The fourth embodiment of the present invention provides an application of the above pegylated ICD inducer-IDO inhibitor conjugate in a single drug delivery system.

[0063] In order to enable those skilled in the art to understand the technical solution of the present invention more clearly, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

Embodiment 1

[0065] (1) Synthesis of 1-MT-Boc:

[0066] Take a clean and dry 5mL ground-mouth round-bottom flask, accurately weigh a certain amount of 57.74mg sodium bicarbonate powder, add 2mL distilled water and 2mLTHF, mix, add a stirrer, stir until the sodium bicarbonate is dissolved, and accurately weigh a certain amount. Amount of 50.9mg NLG8189, 60mg BOC powder, BOC, NLG8189 were sequentially added to a 5mL ground-mouth round bottom flask solution, ice-bathed for 10min, and stirred at room temperature for 24h. Then THF was removed by rotary evaporation, the reaction solution was adjusted to pH=1 with 1mol / L HCl, ethyl acetate was added, and transferred to a separatory funnel. After three extractions, the upper layer solutions were combined, an appropriate amount of anhydrous sodium sulfate was added to remove water, and after standing overnight, ethyl acetate was removed by rotary evaporation to obtain 1-MT-Boc, whose structure was characterized as Figure 1~2 shown.

[0067] (2) ...

Embodiment 2

[0076] diMT-OXA(IV)-PEG 2000 Nanoconjugates inhibit breast tumor growth in vivo

[0077] To evaluate diMT-OXA(IV)-PEG 2000 Efficacy of nanoconjugates in inhibiting tumor growth in vivo in an animal model of breast cancer. Intravenously injecting 4T1 cells into BALB / C mice, 4T1 cells spontaneously generate tumors in BALB / C mice, and the characteristics of this tumor are very similar to breast cancer in humans. BALB / c mice injected with 4T1 cells were given free OXA, free 1-MT, free 1-MT plus OXA, diMT-OXA(IV)-PEG once every three days 2000 Nanoconjugate treatment, and saline control treatment. At the end of the course of treatment, the tumor mass was collected from the experimental mice to measure the tumor volume to evaluate the general anti-tumor effect ( Figure 7 ). Figure 8 showed that the tumors of mice treated with free OXA, free 1-MT, free 1-MT plus OXA were all reduced, while diMT-OXA(IV)-PEG 2000 Tumors in nanoconjugate-treated mice were reduced to more than ab...

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Abstract

The invention discloses a PEGylated ICD inducer-IDO inhibitor nano-conjugate, a preparation method and an application, and its structural formula is as follows: wherein, R is H or the weight average molecular weight is 1000-5000. The PEGylated ICD inducer-IDO inhibitor nanoconjugate provided by the present invention is in an aqueous medium, and the PEGylated drug conjugate can self-assemble into a drug-based nanoconjugate, which can not only reduce MPS Non-specific accumulation in relevant organs, but also improved passive targeting of solid tumors through enhanced permeability and retention, thereby increasing the therapeutic index.

Description

technical field [0001] The invention relates to a pegylated ICD inducer-IDO inhibitor nano conjugate, a preparation method and an application. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Breast cancer is one of the most frequently diagnosed malignancies and the leading cause of cancer death in women. Currently, chemotherapy remains the basis of modern cancer treatment. Specialized chemotherapy, such as oxaliplatin (OXA), can induce true immunogenic cell death (ICD) in cancer cells. ICD-induced immunogenicity can promote intertumoral infiltration of cytotoxic T lymphocytes (CTLs) and accelerate tumor regression. However, breast cancer, known as an immune "cold" tumo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/60A61K31/555A61K31/405A61P35/00
CPCA61K47/60A61K31/555A61K31/405A61P35/00A61K2300/00B82Y5/00
Inventor 姜新义杜微陈晨张晶唐春伟
Owner SHANDONG UNIV
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