Polymer micelle material, preparation and application thereof, and targeted drug of polymer micelle material, preparation and application thereof

A technology of polymer micelles and drugs, which is applied in the direction of drug combinations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of low drug accumulation in tumor sites, non-selectivity of tumor cells, Insufficient tumor targeting effect and other problems, to achieve the effect of improving anti-tumor effect, improving treatment effect, improving efficacy and safety

Inactive Publication Date: 2021-10-08
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the EPR effect of different tumor tissues is quite different. Even the same tumor has different degrees of EPR effect at different stages of development. The overall tumor targeting effect of drugs treated by this effect is insufficient, and the accumulation of drugs in tumor sites lower;
[0011] (2) Traditional nano-drugs are not selective to tumor cells and have low affinity;
[0012] (3) Due to the complex internal environment of the tumor, such as the existence of a hypoxic environment, traditional drugs have problems such as difficult treatment and poor curative effect
[0013] (4) There is a lack of drugs that can regulate the hypoxic microenvironment of tumors and improve the therapeutic effect of hypoxic tumors in the prior art

Method used

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  • Polymer micelle material, preparation and application thereof, and targeted drug of polymer micelle material, preparation and application thereof
  • Polymer micelle material, preparation and application thereof, and targeted drug of polymer micelle material, preparation and application thereof
  • Polymer micelle material, preparation and application thereof, and targeted drug of polymer micelle material, preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Preparation of glucose ligand-type polymer micelles (Glu-PEG-b-P(Asp-g-NIDH)):

[0113] Thiolated glucose (Glu-SH) and maleimide-polyethylene glycol-poly(β-benzyl-L-aspartic acid) (Mal-PEG-b-PBLA) were dissolved in anhydrous DMSO The reaction was stirred overnight at room temperature, and after 24 hours of dialysis, the precipitate was lyophilized to obtain glucose-polyethylene glycol-poly(β-benzyl-L-aspartic acid) (Glu-PEG-b-PBLA).

[0114] Subsequently, glucose-polyethylene glycol-poly(β-benzyl-L-aspartic acid) (Glu-PEG-b-PBLA) was dissolved in acetonitrile at a concentration of 2 mg / mL, and 5-15 equivalents of 0.5M NaOH solution until the solution became clear, stirred vigorously at room temperature for 2 h, dialyzed the reaction solution in deionized water for 24 h, and freeze-dried to obtain polyethylene glycol-polyaspartic acid block copolymer (Glu-PEG-b-PAsp) ;

[0115] Glu-PEG-b-PAsp was dissolved in 2-(N-morpholine)ethanesulfonic acid buffer at pH 6.0, the ca...

Embodiment 2

[0117] Preparation of non-active targeting polymer (PEG-b-P(Asp-g-NIDH)):

[0118] Dissolve polyethylene glycol-poly(β-benzyl-L-aspartic acid) (PEG-b-PBLA) in acetonitrile at a concentration of 2 mg / mL, and then add 5-10 equivalents of 0.5M NaOH solution to The solution became clear, stirred vigorously at room temperature for 2 h, the reaction solution was dialyzed in deionized water for 24 h, and then freeze-dried to obtain PEG-b-PAsp;

[0119] Dissolve PEG-b-PAsp in 2-(N-morpholine)ethanesulfonic acid buffer at pH 6.0, activate the carboxyl group by EDC / NHS reaction, add NI to PEG-b-PAsp, the reaction is at room temperature After 24 hours, the reaction solution was collected, dialyzed with deionized water for 2 days and freeze-dried to obtain the target product PEG-b-P(Asp-g-NIDH), which was characterized by H NMR spectrum 1 H NMR (DMSO) results are attached figure 2 Shown: δ7.69, 7.19(s, CH of midazole), 4.35(m, midazole-CH 2 , -CO-CH-), 3.51 (m, -O-CH 2 CH 2 -O-), 3.2...

Embodiment 3

[0121] Preparation of polymer micelles loaded with CDDP (cis-diammine dichloride) and MnTPPS and related reference substances:

[0122] Weigh each 1.5 mg of PEG-b-P (Asp-g-NIDH) prepared in Example 2 and 0.5 mg of Glu-PEG-b-P (Asp-g-NIDH) prepared in Example 1 as raw materials and dissolve in two In methyl sulfoxide (DMSO), 0.8 mg CDDP and 1.6 mg MnTPPS were simultaneously dissolved in 1 mL Milli-Q ultrapure water. Under ultrasonic conditions, the drug mixture solution was quickly pushed into the DMSO solution of the high molecular polymer, and the ultrasonic was continued for 5 minutes. Subsequently, the obtained micellar solution was transferred to a constant temperature mixer, placed at 37° C., and reacted at 1000 rpm for 72 hours. Ultrafiltration centrifuge tubes (molecular weight cut-off: 35k Da) were added to Milli-Q water for multiple washes to remove free drugs and DMSO, and finally concentrated to obtain polymer micellar GluNPs loaded with CDDP and MnTPPS.

[0123] ...

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Abstract

The invention discloses a polymer micelle material, preparation and application thereof, and a targeted drug of the polymer micelle material, preparation and application thereof, wherein the polymer micelle material has a chemical formula as shown in a formula (1). According to the invention, the polymer micelle material is grafted with a nitroimidazole hypoxia response group on a side chain, and surface glucose target molecule modification is further carried out in some specific embodiments, so that the polymer micelle material not only has the performance of actively targeting tumors, but also has hypoxic microenvironment response, can release drugs in a hypoxic microenvironment, and realizes efficient drug delivery and tumor treatment.

Description

technical field [0001] The invention relates to the technical field of medical polymer materials, in particular to the technical field of targeted drug delivery materials. Background technique [0002] Cancer refers to all malignant tumors in medicine. According to the latest global cancer burden data released by the International Agency for Research on Cancer of the World Health Organization in 2020, there are 19.29 million new cancer cases worldwide, and the new cases in China account for about one-fifth of them; the global cancer death toll is 996 There are 3 million cancer deaths in China. Cancer is a major killer that threatens human life and health in today's society, and it is also one of the great challenges facing the modern medical field. At present, traditional chemotherapy drugs have no selectivity for tumor cells, have poor curative effect, and cause toxic and side effects to normal organs and tissues. Therefore, it has become a research hotspot in the field ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00A61K9/107A61K33/243A61K47/34A61P35/00A61P35/04
CPCC08G81/00A61K47/34A61K9/1075A61K33/243A61P35/00A61P35/04A61K2300/00
Inventor 米鹏王瑶
Owner SICHUAN UNIV
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