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Preparation method and application of a kind of active oxygen responsive material pam-sh

A PAM-SH, responsive technology, applied in the direction of organic active ingredients, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., to achieve good biocompatibility and improve effect.

Active Publication Date: 2022-03-22
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, hepatotoxicity and muscle pain are known serious side effects during simvastatin ad libitum administration, and the patient had to discontinue treatment due to rhabdomyolysis

Method used

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  • Preparation method and application of a kind of active oxygen responsive material pam-sh
  • Preparation method and application of a kind of active oxygen responsive material pam-sh
  • Preparation method and application of a kind of active oxygen responsive material pam-sh

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Experimental program
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Effect test

Embodiment 1

[0038] Example 1: Synthesis of active oxygen responsive material PAM-SH

[0039] 1) Synthesis of -0.5G PAMAM

[0040] PAMAM is synthesized by a divergent method, involving two-step iterative reactions, using Michael addition and amidation reactions to gradually diverge to the periphery, resulting in branched (generational) concentric shells around the central initiator core. First, anhydrous methanol (200 mL) containing methyl acrylate (MA, 146 mL, 1.6 mol) was slowly dropped into ethylenediamine (EDA, 13 mL, 0.2 mol) in an ice bath to react for 30 min, and then reacted at room temperature for 18 h . All the above reactions were performed at N 2 under protection. Finally, methanol and excess MA were removed by rotary evaporation under reduced pressure, and vacuum-dried for 24 h to obtain a light yellow viscous liquid (-0.5G PAMAM, 79 g, 97%).

[0041] 2) Synthesis of 0G PAMAM

[0042]Under the condition of ice bath, EDA-containing anhydrous methanol (140mL, 2.1mol) was sl...

Embodiment 2

[0051] Embodiment 2: Preparation of SA PAM nanoparticles

[0052] Dissolve 0.456 g of simvastatin in 11 mL of ethanol, add NaOH (17 mL, 0.1 M), react at 50° C. for 2 h, and adjust the pH of the reaction solution to neutral with hydrochloric acid. The ethanol in the reaction solution was removed by rotary evaporation, and the SA was extracted by adding n-butanol. The organic phase was rotovaped and dried in vacuo to yield 0.402 g of SA. Subsequently, SA PAM was prepared with a mass ratio of PAM-SH to SA of 5:10. The specific steps are: in N 2 Under protection, 0.1M NaBH 4 Added into deionized water containing 5 mg of PAM-SH, stirred at room temperature for 3 h, adjusted the solution to neutral with 0.1 M HCl, slowly added 2 mL of DMSO solution containing 10 mg of SA into the reaction solution, and reacted at room temperature for 5 h. Finally, SA PAM was obtained by dialysis against deionized water for 2 days using a dialysis bag (MWCO 1.0 kDa). image 3 is the synthetic ro...

Embodiment 3

[0053] Embodiment 3: drug loading and drug release

[0054] Use ultraviolet-visible spectrometer (UV-2450, Shimadzu Corporation of Japan) to detect H at 243nm. 2 o 2 SA content in SA PAM in deionized water. After freeze-drying the SA PAM solution, weigh a certain amount of SA PAM powder and dissolve it in deionized water containing hydrogen peroxide. After high-speed centrifugation, transfer the supernatant to a quartz cuvette, and observe the concentration of SA at 25°C. UV absorption peak, and the drug loading was obtained according to the established standard curve. In vitro drug release studies were performed using dialysis bags. Briefly, an equal amount of SA PAM solution contained in a dialysis bag (MWCO 3.5 kDa) was immersed in 2 o 2 The volume of each sample was 68 mL in PBS (pH 7.4) (0, 2.5, 5, 7.5 and 10 mM). The experiment was shaken gently on a shaker in a dark environment at 37°C. At predetermined time points, 3 mL of dialysate was withdrawn for UV assay to...

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Abstract

The preparation method and application of an active oxygen responsive material PAM‑SH of the present invention belong to the technical field of nanomaterial preparation. The preparation steps include 1) synthesis of 0.5G PAMAM, 2) synthesis of 0G PAMAM, 3) synthesis of 0.5G PAMAM, 4) synthesis of 4.0G PAMAM, 5) synthesis of PAM‑SH, etc. The nanoparticle prepared by the invention has the characteristic of specific response to hydrogen peroxide, can not only reduce the toxicity of simvastatin acid, but also improve the therapeutic effect by consuming active oxygen through simvastatin acid.

Description

technical field [0001] The invention belongs to the technical field of nanomaterial preparation, and in particular relates to the preparation and application of a nanoparticle capable of responding to active oxygen (ROS) and capable of specific drug release. Background technique [0002] Cardiovascular diseases (CVDs) have high morbidity and mortality rates in China and the world, and are listed as the number one cause of death. Atherosclerosis (AS) is an important pathological basis of cardiovascular diseases, accounting for 61% of cardiovascular disease deaths. Inflammation can promote the production of excess reactive oxygen species (ROS), so the special ROS microenvironment of the plaque can be used to design drug delivery systems to trigger drug release. [0003] As we all know, functional nanoparticles are a revolutionary disease treatment method and have been widely used in the field of biomedicine. Cationic polyamidoamine (PAMAM) dendrimers are the first class of c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G73/02A61K31/366A61K47/59A61K47/69A61P7/02A61P9/10
CPCC08G73/028A61K47/595A61K47/6935A61K31/366A61P9/10A61P7/02
Inventor 李亚鹏沈美丽刘顺武小东李少静姚顺雨
Owner JILIN UNIV
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