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Bioadhesive nanoparticle for treating gastrointestinal diseases and preparation method of bioadhesive nanoparticle

A technology for gastrointestinal diseases and bioadhesion, which is used in medical preparations without active ingredients, medical preparations containing active ingredients, and drug combinations, etc. It can solve esophageal surface damage, low compliance, and patients unable to drink water, etc. problems, to achieve the effect of reducing side effects and improving the therapeutic effect

Active Publication Date: 2022-01-04
中山大学深圳 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The traditional solution is to use adhesive solid preparations, which can extend the residence time of the drug in the esophagus to 1.5 hours, but the solid preparations are likely to cause damage to the surface of the esophagus, causing secondary damage to patients with esophageal diseases; and taking the solid preparations Afterwards, the patient cannot drink or eat, and the compliance is low

Method used

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  • Bioadhesive nanoparticle for treating gastrointestinal diseases and preparation method of bioadhesive nanoparticle
  • Bioadhesive nanoparticle for treating gastrointestinal diseases and preparation method of bioadhesive nanoparticle
  • Bioadhesive nanoparticle for treating gastrointestinal diseases and preparation method of bioadhesive nanoparticle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Preparation of Example 1 Bioadhesive Nanoparticles BNPs (Dye Loaded)

[0032] Prepare BNPs by emulsion method:

[0033] (1) Synthesis of HPG (hyperbranched polyglycidyl ether):

[0034] Under the protection of argon, add 4.67mmol 1,1,1-trimethylolpropane (TMP) into a flask in an oil bath at 95°C, after complete dissolution, add 1.4mmol KOCH 3 (Potassium methylate), connect the flask to a vacuum pump, and evacuate the biscuits to a vacuum state, then fill with argon after 10 minutes, and fill the entire flask all the time, then add 25mL glycidol in 12 and a half hours through a micro-syringe pump to obtain Crude HPG. Dissolve crude HPG in methanol and precipitate with acetone, repeat this process two or three times to purify HPG; then dialyze HPG in ultrapure water through a dialysis bag (500-1000D) to remove some small molecular weight HPG, every 5 Change the water twice every hour; finally, add acetone to precipitate HPG again, and dry HPG under vacuum at 85°C for 8...

Embodiment 2

[0042] Example 2 Preparation of Bioadhesive Nanoparticles NFDP / BNPs (Drug Loading, NFDP / BNPs for short)

[0043] The preparation method is the same as that in Example 1, except that PLA-Cy5 is replaced by the drug NFDP (nifedipine).

experiment example 1

[0044] Experimental Example 1 Investigation of the residence time of fluorescent bioadhesive nanoparticles loaded in the esophagus of rats

[0045] In this embodiment, NNPs (nonadhesive nanoparticles) refer to non-bioadhesive nanoparticles loaded with dyes, and BNPs (bio-adhesive nanoparticles) refer to bioadhesive nanoparticles loaded with dyes.

[0046] In order to evaluate the retention and distribution of the dye-loaded NNPs prepared in Example 1 on the esophagus in vivo (with the dye-loaded non-adhesive nanoparticle NNPs prepared in Example 1 as a control), 1 mL concentration of 2 mg / mL of dye-loaded NNPs and dye-loaded BNPs were fed into the esophagus of male SD rats (purchased from Beijing Speifu Biotechnology Co., Ltd., fed for 9-10 weeks to a size of about 300 g) through a gavage needle. And at different time points (0, 1, 2, 4, 6, 10 h), the rats were euthanized under carbon dioxide environment, and then the esophagus was quickly removed, and the small animal live i...

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Abstract

The invention belongs to the technical field of drug carrier materials, and particularly relates to a bioadhesive nanoparticle for treating gastrointestinal diseases and a preparation method of the bioadhesive nanoparticle. A non-bioadhesive degradable nanoparticle drug / NNPs is prepared from drugs for treating gastrointestinal diseases and biodegradable PLA and HPG; and the drug / NNPs is oxidized and reduced by sodium periodate to become a biodegradable nanoparticle drug / BNPs with biological viscosity, and the prepared bioadhesive nanoparticle BNPs can be connected with proteins of a gastrointestinal tract system, so that the bioadhesive nanoparticle BNPs can be adhered to tissue, slowly release the drug, realize targeted release of the drug in the esophagus, further play a better treatment effect, and reduces side effects.

Description

technical field [0001] The invention belongs to the technical field of drug carrier materials, and in particular relates to a bioadhesive nanoparticle for treating gastrointestinal diseases and a preparation method thereof. Background technique [0002] Gastrointestinal diseases, such as gastroesophageal reflux, achalasia (the common type is esophageal cardia stenosis), etc., are usually chronic and localized. For these local diseases, if systemic administration is used, not only the therapeutic effect is low, but also the toxicity is high. Therefore, choosing a local drug delivery method can reduce drug side effects and improve drug efficacy. [0003] However, when the drug is delivered from the oral cavity to the stomach, the typical transit time of the drug through the esophagus is only 10-14 seconds, which makes it difficult to make the drug stay in the esophagus to achieve the effect of local delivery. The traditional solution is to use adhesive solid preparations, wh...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K47/34A61K45/06A61K31/4422A61P1/00C08G81/00C08G65/28
CPCA61K9/1647A61K45/06A61K31/4422A61P1/00C08G81/00C08G65/2609
Inventor 麦扬欧阳亚琪刘洋邓扬
Owner 中山大学深圳
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