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Pharmacosome hydrogel patch for GSH concentration responsive treatment of hyperthyroidism and preparation method thereof

A technology of hydrogel patch and thyroid function, which is applied in the direction of medical formula, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., which can solve the problem of large oral doses of drugs, frequent taking times, and short biological half-life and other issues, to achieve the effect of high compliance, optimal drug selection, and high encapsulation rate

Active Publication Date: 2020-11-27
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the short biological half-life of methimazole, the large oral dose of the drug, and frequent administration may lead to serious consequences, there have been reports of death from acute liver failure caused by methimazole

Method used

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  • Pharmacosome hydrogel patch for GSH concentration responsive treatment of hyperthyroidism and preparation method thereof
  • Pharmacosome hydrogel patch for GSH concentration responsive treatment of hyperthyroidism and preparation method thereof
  • Pharmacosome hydrogel patch for GSH concentration responsive treatment of hyperthyroidism and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] The preparation of embodiment 1 drug plasmid:

[0046] (1) Preparation of 3-[(1-methyl-1H-imidazol-2-yl)thio]-2-acrylic acid (methimazole acrylic acid, MMI-AA)

[0047] Methimazole (30mmol) was dissolved in methanol (0.5mol), sodium methoxide (10mmol) was added thereto under stirring until the methimazole was completely dissolved, and then propiolic acid (10mmol) was added therein. Reaction temperature: 50°C, under nitrogen protection, and react under reflux for 100 hours. After the reaction, use a rotary evaporator to evaporate the reaction solution at 32°C for 60 minutes to obtain a thick white liquid; freeze-dry the thick white liquid for 50 hours, and obtain MMI-AA (white flake solid) after lyophilization .

[0048] (2) Preparation of 3-[(1-methyl-1H-imidazol-2-yl)thio]-2-acrylic acid-dodecyl (methimazole acrylate dodecyl, MMI-AA-OLa)

[0049] Dissolve methimazole acrylic acid (9mmol) and EDC (27mmol) in DMF (260mmol) and activate for 20min with stirring. After 2...

Embodiment 2

[0051] The preparation method is the same as in Example 1, except that n-octanol and methimazole acrylic acid are used to obtain methimazole n-octyl acrylate MMI-AA-OCa.

Embodiment 3

[0053] The preparation method is the same as in Example 1, except that stearyl alcohol and methimazole acrylic acid are used to obtain methimazole acrylate stearyl MMI-AA-OSt.

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Abstract

The invention relates to a pharmacosome hydrogel patch for GSH concentration responsive treatment of hyperthyroidism and a preparation method thereof. The patch comprises a polymer matrix, a methimazole pharmacosome and auxiliary materials. The methimazole pharmacosome hydrogel patch provided by the invention can be used for transdermal drug delivery through thyroid lesion sites, and the pharmacosome in the patch has good GSH responsiveness, and can respond to intracellular glutathione concentration stimulation and realize intelligent release of drugs.

Description

technical field [0001] The invention relates to a methimazole drug plastid hydrogel patch, in particular to a preparation method and application of a GSH concentration-responsive methimazole drug plastid hydrogel patch. Background technique [0002] Methimazole (MMI) is an imidazole antithyroid drug, its mechanism of action is to inhibit the peroxidase in the thyroid, hinder the oxidation of iodide absorbed into the thyroid and the coupling of tyrosine, and then hinder the thyroxine ( T4) and triiodothyronine (T3) synthesis. MMI does not affect the absorption of iodine and the release of synthesized hormones. Studies have shown that MMI accumulates in the thyroid after oral absorption. Only when it enters the thyroid can it exert its therapeutic effect of inhibiting thyroxine synthesis. The strength of the effect depends on the local drug concentration in the thyroid. Due to the strong hydrophilicity of MMI, it is difficult to pass through the thyroid bubble membrane, resul...

Claims

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Application Information

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IPC IPC(8): A61K9/70A61K9/06A61K47/10A61K47/22A61K47/54A61K31/4164A61P5/16
CPCA61K9/7023A61K9/0004A61K9/06A61K47/10A61K47/22A61K47/542A61K47/54A61K31/4164A61P5/16
Inventor 戴红莲代悦
Owner WUHAN UNIV OF TECH
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