Pharmaceutical composition for mild photothermal therapy of tumors as well as preparation method and application of pharmaceutical composition

A composition and pharmaceutical technology, which is applied in the field of pharmaceutical composition and its preparation for mild and photothermal therapy of tumors, can solve the problems of tissue damage and stimulate cancer risk, so as to improve compliance, improve anti-tumor effect, and inhibit protective autoimmunity. The effect of phagocytosis

Active Publication Date: 2022-03-11
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, in order to improve the effect of photothermal killing of tumor cells, it is often necessary to increase the irradiation intensity or prolong the irradiation time. However, excessive irradiation will cause damage to normal tissues and stimulate other cancer risks.

Method used

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  • Pharmaceutical composition for mild photothermal therapy of tumors as well as preparation method and application of pharmaceutical composition
  • Pharmaceutical composition for mild photothermal therapy of tumors as well as preparation method and application of pharmaceutical composition
  • Pharmaceutical composition for mild photothermal therapy of tumors as well as preparation method and application of pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Preparation and Characterization of 4-methoxybenzoyloydiamine-carboxylated dextran-hexadecan / IR820 + 3-MA pharmacy composition

[0058] (1) Preparation of pharmaceutical compositions

[0059] 1) The 2 g of glucan is completely dissolved in 24 ml anhydrous dimethyl sulfoxide to obtain a dextran solution; 10 mg of DMAP catalyst is added to 30 minutes under ice bath conditions, 334 mg butaric acid anhydride, stirred to complete solvent, room temperature Reaction 24h. The reaction liquid was added dropwise to 120 ml of icy ethanol to form a precipitate, and the filtration was filtered and continued for 2 times, and the precipitate was collected, and the distilled water was recollected. (DEX-COOH);

[0060] 2) Take 200 mg of carboxylated dextran, add 10 ml of distilled water to dissolve 170 mGNHS under ice bath, 260 mgEDC catalyst to activate 30 min, 20 mg of hexadecam is dissolved with 10 ml of ethanol, adding to a carboxyl glucan solution, room temperature After 24 h, 50 ° C...

Embodiment 2

[0075] Preparation and characterization of 4-methoxybenzoyamine-carboxylated dextran-oxadamine / IR780 + hydroxyanoquine

[0076] (1) Preparation of pharmaceutical compositions

[0077] 1) The 2 g of glucan is completely dissolved in 24 ml anhydrous dimethyl sulfoxide to obtain a dextran solution; 10 mg of DMAP catalyst is added to 30 minutes under ice bath conditions, 334 mg butaric acid anhydride, stirred to complete solvent, room temperature The reaction was transferred for 24 h; the reaction liquid was added dropwise to 120 ml of icy ethanol to form a precipitate, and the filtration was filtered and then washed twice with ice ethanol, and the precipitate was collected, and the distillation water was reconstituted. Dex-cooh;

[0078] 2) Take 200 mg of carboxylated dextran, add 10 ml of distilled water, and 170 mGNHS under ice bath, 260 mGEDc catalyst is activated for 30 min, 14.8 mg of oxanine is dissolved with 10 ml of ethanol, and it is added dropwise to the carboxylated dext...

Embodiment 3

[0094] Preparation and Characterization of 4-methoxybenzoatlamine-carboxylated glucan-deoxycholic / indole cream green +

[0095] (1) Preparation of pharmaceutical compositions

[0096] 1) The 2 g of glucan is completely dissolved in 24 ml anhydrous dimethyl sulfoxide to obtain a dextran solution; 10 mg of DMAP catalyst is added to 30 minutes under ice bath conditions, 334 mg butaric acid anhydride, stirred to complete solvent, room temperature Reaction 24h. The reaction liquid was added dropwise to 120 ml of icy ethanol to form a precipitate, and the filtration was filtered and continued for 2 times, and the precipitate was collected, and the distilled water was recollected. (DEX-COOH);

[0097] 2) Take 1 g of deoxychol to completely dissolve in 15 ml of tetrahydrofuran, add 0.3814 g, 0.6272 Gdcc, and then dissolved at room temperature for 12h, and remove the resulting white precipitate, the filtrate is added to obtain precipitate filtration after 5 times the amount of n-hexane, ...

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Abstract

The invention provides a pharmaceutical composition for mild photothermal therapy of tumors as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition is composed of a dual-targeting amphiphilic glucan derivative carrier, a material (PTA) with photo-thermal conversion performance and an autophagy inhibitor. The dual-targeting amphiphilic glucan derivative carrier can be self-assembled in water to form nano-micelles, and is physically loaded with PTA and an autophagy inhibitor for tumor photothermal therapy. The preparation is mainly characterized in that: 1) the preparation has active dual-targeting capability of tumor cells and tumor-related fibroblasts, and can efficiently enter the cells through the action of receptor ligands, so that the transfer efficiency of the preparation is improved; 2) under the irradiation of 808nm laser, PTA absorbs light energy and efficiently converts the light energy into heat, and the autophagy inhibitor inhibits the autophagy behavior of tumor cells and sensibilizes photo-thermal, so that an excellent mild photo-thermal treatment effect is realized, and the physical barrier of a tumor matrix can be weakened; tumor photothermal can further induce tumor cells to generate immunogenic cell death, generated tumor fragments can further activate an immune system, and the tumor photothermal treatment effect is greatly improved.

Description

Technical field [0001] The present invention belongs to the field of pharmaceutical preparations, and involves a pharmaceutical composition for tumor temperature and photothermal treatment and a preparation method thereof. Background technique [0002] Solid tumor microenvironment, that is, the high fibroblast hyperplasia and strong immune inhibition in solid tumors are the culprit leading to anti-tumor drugs and related immunogenic preparations in solid tumors. On the one hand, there is a large number of tumor-related fibroblasts (CAFs) in tumor microefficients, excessively activated under a large number of cytokines such as transformed growth factor-β (TGF-β), resulting in deposition of extracellular matrix (ECM), forming A dense matrix barrier. On the other hand, there are a variety of inhibitory cytokines and immune cells in the micro-ring in immunosuppressive, and all-roundly inhibition in multiple key nodes such as immunochages, forming a shelter of helping tumor cell immun...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/02A61K9/107A61K31/4706A61K41/00A61K45/06A61K47/36A61K47/54A61P35/00
CPCC08B37/0006A61K41/0052A61K45/06A61K9/1075A61K47/36A61K47/54A61K31/4706A61P35/00A61K2300/00Y02A50/30
Inventor 霍美蓉刘楠张盼周新源
Owner CHINA PHARM UNIV
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