Preparation method, product and application of a pH-sensitive nano-sized bcl-2 selective inhibitor

A technology of bcl-2 selectivity, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc., can solve the limitation of clinical treatment of Bcl-2 selective inhibitors, and cannot be too large To maximize the efficacy of the drug, lack of intracellular targeting, etc., to achieve good clinical transformation possibility, good biocompatibility, and the effect of improving drug efficacy

Active Publication Date: 2020-02-28
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Bcl-2 selective inhibitors are poorly water soluble and lack intracellular targeting
Therefore, the clinical treatment of Bcl-2 selective inhibitors is greatly limited, and its efficacy cannot be brought into play to a large extent.

Method used

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  • Preparation method, product and application of a pH-sensitive nano-sized bcl-2 selective inhibitor
  • Preparation method, product and application of a pH-sensitive nano-sized bcl-2 selective inhibitor
  • Preparation method, product and application of a pH-sensitive nano-sized bcl-2 selective inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] 1) Synthesis of a pH-sensitive amphiphilic polymer: 0.2 g of ethylene glycol aspartate benzyl ester copolymer was dissolved in 5 ml of N,N-dimethylformamide, and 1 g of 1-( 3-aminopropyl)imidazole. Under the protection of argon, stir at room temperature for 12 hours. After the reaction, the solution was dropped into 0.1N hydrochloric acid solution at 4°C, dialyzed in 0.01N hydrochloric acid solution, and freeze-dried to obtain imidazole-modified ethylene glycol aspartate benzyl ester copolymer. NMR structural characterization of the prepared pH-sensitive amphiphilic polymer, such as figure 1 shown.

[0041] 2) Preparation of a pH-sensitive nano-sized Bcl-2 selective inhibitor: 10 mg of the imidazole-modified ethylene glycol aspartate benzyl ester copolymer obtained in step 1) was dissolved in the Bcl-2 selective inhibitor ABT-1995 mg In 3ml of dimethyl sulfoxide and 1ml of methanol, stirring, rotary evaporation to remove methanol. The solution was then dialyzed for ...

Embodiment 2

[0044]1) Synthesis of a pH-sensitive amphiphilic polymer: 0.2 g of octadecylamine aspartate benzyl ester copolymer was dissolved in 5 ml of dimethyl sulfoxide, and 1 g of 1-(3-aminopropyl base) piperidine. Under the protection of argon, stir at room temperature for 12 hours. After the reaction, the solution was dropped into 0.1N hydrochloric acid solution at 4°C, dialyzed in 0.01N hydrochloric acid solution, and freeze-dried to obtain a piperidine-modified octadecylamineaspartate benzyl ester copolymer.

[0045] 2) Preparation of a pH-sensitive nano-sized Bcl-2 selective inhibitor: the Bcl-2 selective inhibitor ABT-1995mg and the piperidine-modified octadecylamine aspartate benzyl ester copolymer 15mg obtained in step 1) Dissolve in 3ml dimethyl sulfoxide and 1ml methanol, stir, and remove methanol by rotary evaporation. The solution was then dialyzed for two days, and excess polymer was removed by centrifugation, resulting in a pH-sensitive nanosized Bcl-2 selective inhibit...

Embodiment 3

[0047] 1) Synthesis of pH-sensitive amphiphilic polymers: 0.2 g of ethylene glycol benzyl glutamate copolymer was dissolved in 5 ml of dimethyl sulfoxide, and 1 g of 1-(3-aminopropyl ) imidazole. Under the protection of argon, stir at room temperature for 12 hours. After the reaction, the solution was dropped into 0.1N hydrochloric acid solution at 4°C, dialyzed in 0.01N hydrochloric acid solution, and freeze-dried to obtain imidazole-modified ethylene glycol benzyl glutamate copolymer.

[0048] 2) Preparation of a pH-sensitive nano-sized Bcl-2 selective inhibitor: 15 mg of the imidazole-modified ethylene glycol benzyl glutamate copolymer obtained in the Bcl-2 selective inhibitor ABT-1995 mg and step 1) was dissolved in 3ml of dimethylformamide and 1ml of methanol, stirring, rotary evaporation to remove methanol. The solution was then dialyzed for two days, and excess polymer was removed by centrifugation, resulting in a pH-sensitive nanosized Bcl-2 selective inhibitor.

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Abstract

The invention relates to a preparation method of a pH-sensitive nano Bcl-2 selective inhibitor. The preparation method comprises the following steps: 1) dissolving amphiphilic macromolecules into a good solvent, adding a modifier with a pH responsive radical, carrying out a stirring reaction, and dialyzing to obtain a pH-sensitive amphiphilic polymer; 2) dissolving the pH-sensitive amphiphilic polymer in the step 1) and a Bcl-2 selective inhibitor into the good solvent for the stirring reaction to obtain a mixed solution; 3) carrying out rotary evaporation, dialysis and centrifugation on the mixed solution in the step 2) to obtain the pH-sensitive nano Bcl-2 selective inhibitor. The invention also relates to the prepared pH-sensitive nano Bcl-2 selective inhibitor and application thereof. The preparation reaction system is mild, the conditions are controllable, and the prepared material is good in biocompatibility and has good clinical conversion possibility.

Description

technical field [0001] The invention relates to the field of preparation of Bcl-2 selective inhibitors, in particular to a preparation method, product and application of pH-sensitive nanometerized Bcl-2 selective inhibitors. Background technique [0002] Asthma is a serious respiratory disease that affects millions of people worldwide, and the number of patients is on the rise. Asthma is an inflammatory disease of the airways with multiple subtypes in which the innate and adaptive immune systems interact to cause recruitment of inflammatory cells, airway hyperresponsiveness, mucus hypersecretion, and airway remodeling. [0003] Currently, glucocorticoids or a combination of long-term short-acting β-agonist bronchodilators (LABA or SABA) and leukotriene antagonists (LTRAs) as the first-line treatment for asthma can play a good role in most patients with asthma. treatment effect. However, there are still some asthma patients whose condition cannot be effectively controlled. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/54A61K45/00A61K31/787A61P11/06
CPCA61K31/787A61K45/00
Inventor 凌代舜李方园李锐清沈华浩应颂敏
Owner ZHEJIANG UNIV
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