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Bilirubin nanoparticles for treating acute pancreatitis and preparation method thereof

A technology for acute pancreatitis and nanoparticles, which is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, and pharmaceutical formulas, etc. It is easy to operate, prolong the residence time, and have good biocompatibility.

Active Publication Date: 2019-07-30
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] And in view of the poor stability and strong fat solubility of bilirubin, how to optimize the prescription of silk fibroin nano-preparation so that it can play a role in the treatment of entrapped drugs is still a technical problem
[0006] At present, there is no report on the use of bilirubin for acute pancreatitis, and there is no report on the use of bilirubin, silk fibroin and ceramide to prepare nanoparticles, and there is no report on the use of ceramide and genipin in combination with silk fibroin. Related reports on the preparation of nanoparticles loaded with bilirubin

Method used

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  • Bilirubin nanoparticles for treating acute pancreatitis and preparation method thereof
  • Bilirubin nanoparticles for treating acute pancreatitis and preparation method thereof
  • Bilirubin nanoparticles for treating acute pancreatitis and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The preparation of embodiment 1 bilirubin nanoparticles

[0035] After silkworm cocoons are degummed with sodium bicarbonate weak alkali solution, they are completely dissolved with lithium bromide solution, and regenerated silk fibroin is obtained after dialysis with deionized water; 10 mg of bilirubin, 1 mg of genipin, and 10 mg of ceramide phosphoethanolamine are dissolved in 2 ml of DMSO , and then add 7ml of acetone to mix to obtain the organic phase; take 50mg of silk fibroin and dissolve it in 1ml of pure water, centrifuge at 4000rpm for 5min and take the supernatant as the aqueous phase; mix the aqueous phase and the organic phase at 50°C for 6h, dialyze Removing the organic solvent; diluting the obtained nanosuspension with pure water to obtain bilirubin nanoparticles ①.

[0036] The preparation method of bilirubin nanoparticles ② is the same as this method, the difference is that ceramide phosphoethanolamine is replaced with equal mass of ceramide phosphorylch...

Embodiment 2

[0046] The characterization of embodiment 2 bilirubin nanoparticles

[0047] 2.1 Particle size and Zeta potential

[0048]The bilirubin nanoparticles prepared in Example 1 were taken, and the average size and Zeta potential of the nanoparticles were detected by dynamic light scattering. The morphological examination of bilirubin nanoparticles① was carried out by transmission electron microscopy. Specifically, after diluting bilirubin nanoparticles to an appropriate concentration, the samples were prepared by dropping on a copper grid coated with a carbon film, and then examined under a transmission electron microscope. Observe the shape of the sample.

[0049] The particle size and Zeta potential are shown in Table 1. The results showed that the particle size of bilirubin nanoparticles ① was 184.34±10.78, and the PDI value was 0.083. The particle size of bilirubin nanoparticles② was 176.39±8.73, and the PDI value was 0.102. PDI represents the uniformity of the particle size...

Embodiment 3

[0062] Example 3 Therapeutic effect of bilirubin nanoparticles on acute pancreatitis

[0063] 3.1 Establishment of acute pancreatitis rat model

[0064] 5-week-old male SD rats were randomly divided into control group, model group and drug intervention group. Before the experiment, the rats were adaptively fed for 1 week before the experiment, and fasted for 12 hours before modeling, and water was not allowed. The mouse was given two intraperitoneal injections of arginine (2.5 mg / ml administration) at intervals of 1 hour, and after the second administration was completed, the amylase increased, which meant that the model was established successfully. After the experiment (that is, 24 hours after the start of modeling), blood was collected from the orbit to collect and separate serum, and stored at -80°C for subsequent measurement of amylase lipase levels. ELISA measured serum inflammatory factors TNF-α, IL-6 levels and The level of the anti-inflammatory factor IL-10; After t...

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Abstract

The invention discloses bilirubin nanoparticles for treating acute pancreatitis and a preparation method thereof. The nanoparticles are mainly composed of silk fibroin, bilirubin, genipin and ceramide. The method comprises the steps that firstly, the bilirubin, the genipin and the ceramide are dissolved in a mixed organic reagent; secondly, the silk fibroin is dissolved in an aqueous solution, then the mixed solution of the bilirubin, the genipin and the ceramide is slowly added into the silk fibroin solution dropwise and continuously stirred, the organic solvent is removed through dialysis, and an obtained nanoparticle suspension is diluted with pure water to obtain the bilirubin nanoparticles. The bilirubin nanoparticles can be used for treating acute pancreatitis and relieving tissue edema caused by pancreatitis, can be applied to preparation of medicines for treating acute pancreatitis, and has wide clinical application prospects.

Description

technical field [0001] The invention belongs to the technical field of nano drug carrier, and in particular relates to a nano particle for treating acute pancreatitis and its preparation. Background technique [0002] Acute pancreatitis is an inflammatory disease of the pancreas. The most common symptom is acute abdominal pain. The severe inflammatory response can cause multiple organ failure. Studies have confirmed that serum amylase and lipase in patients with acute pancreas are three to four times higher than normal. Even with prompt treatment, about 75% of patients experience mild pancreatic damage. It is worth emphasizing that about 25% of patients may develop serious complications, while 50% of patients even die from systemic complications. In recent decades, it is particularly urgent to find safe and effective means to treat acute pancreatitis, but there is little progress in clinical treatment of acute pancreatitis. The exact mechanism of regulating the important ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K31/409A61K47/42A61K47/18A61K47/24A61P1/18
CPCA61K9/5123A61K9/5169A61K31/409A61P1/18
Inventor 姚情赵应征鲁翠涛徐荷林寇龙发江雪黄志伟郑雅文林蒙婷
Owner WENZHOU MEDICAL UNIV
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