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Application of nano-micelle-hydrogel preparation of HDAC inhibitor with double targets in medicine for treating acute kidney injury

A technology of acute kidney injury and nano micelles, which is applied in the field of biomedicine to achieve the effects of alleviating renal tubular necrosis, improving renal tubular mesangial sclerosis, and alleviating renal tubular dilation

Active Publication Date: 2021-10-01
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Today's standard therapy for acute kidney injury is renin-angiotensin-aldosterone therapy, but the incidence of the disease is on the rise, so there is an urgent need to find alternative innovative therapies

Method used

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  • Application of nano-micelle-hydrogel preparation of HDAC inhibitor with double targets in medicine for treating acute kidney injury
  • Application of nano-micelle-hydrogel preparation of HDAC inhibitor with double targets in medicine for treating acute kidney injury
  • Application of nano-micelle-hydrogel preparation of HDAC inhibitor with double targets in medicine for treating acute kidney injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1 carries the preparation of SAHA-Ac nano micelles

[0041] 1. Experimental method:

[0042] 1. Prepare a mother solution with a drug concentration of 10 mg / mL, that is, dissolve 22 mg of the drug in 2.2 mL of DMSO. Take the polymer material mPEG-b-PCL (10000:8000) as the carrier, the mass ratio of drug to material is 1:10, add DMSO to dilute to 1 mL, dissolve and mix well under ultrasonic.

[0043] 2. Take another 19mL of ultra-pure water in the sample bottle, add a rod-shaped magnet to the bottle, and then place the sample bottle on a constant temperature electric heating mantle to heat and stir. The assembly temperature was set at 40 °C.

[0044] 3. Use a syringe to take the above mother liquor and add it dropwise to ultrapure water at a rate of 2 seconds per drop. After the addition is complete, continue stirring at 800 rpm for 10 minutes, and finally cool slowly at room temperature.

[0045] 4. Transfer the micellar solution to a 3500Da dialysis bag, ...

Embodiment 2

[0058] Example 2 Preparation and Characterization of Injectable Aseptic Chitosan Thermosensitive Hydrogel

[0059] 1. Experimental method:

[0060] 1. Preparation of chitosan (CS) solution with a mass fraction of 2%: Dissolve 200 mg of CS powder sterilized by high temperature and high pressure (120 ° C, 15 min) in 10 mL of 0.1 M HCl, keep stirring until completely dissolved, and store in an ice bath until use.

[0061] 2. Preparation of 56% sodium β-glycerophosphate (β-GP) solution: 0.56 g of β-GP was dissolved in 1 mL of triple-distilled water, and sterilized by filtration with a 0.22 μm microporous membrane.

[0062] 3. Preparation of drug-loaded micelles hydrogel: add 0.1mL drug-loaded micelles to 0.8mL CS solution, then add 0.1mL β-GP solution, with a volume ratio of CS:β-GP:drug-loaded micelles=8 :1:1 Mix well.

[0063] 4. Concentration and aseptic treatment of the micellar solution: soak the ultrafiltration centrifuge tube with 70% (v / v) isopropanol solution for 15 mi...

Embodiment 3

[0068] Example 3. In vitro inhibition experiment of SAHA-Ac on HDAC2 activation

[0069] 1. Experimental cells:

[0070] HK-2 renal papilloma cell line, placed in RPMI1640 medium with 10% fetal bovine serum, at 37°C, 5% CO 2 Cultured in a constant temperature incubator, subcultured once every two to three days, and the cells that had expired in logarithmic growth were taken for experiments.

[0071] 2. Experimental group:

[0072] 1. Blank group (Control): no drug treatment

[0073] 2. Positive control group (H 2 o 2 1mmol / L): add 1mmol / L H 2 o 2 Activate cells to produce large amounts of p-HDAC2

[0074] 3. Experimental group treated with 5μM SAHA-Ac (H+SAHA-Ac 5μM): 1mmol / L H 2 o 2 +SAHA-Ac 5μM

[0075] 4. Experimental group treated with 5μM SAHA (H+SAHA 5μM): 1mmol / L H 2 o 2 +SAHA 5 μM

[0076] 3. Experimental method

[0077] Add the corresponding reagents to the cells according to the experimental group, and perform protein separation and western blotting ex...

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Abstract

The invention provides an application of a nano-micelle-hydrogel preparation of an HDAC inhibitor with double targets in a medicine for treating acute kidney injury. The S-SAHA small molecule is a known HDAC inhibitor; the invention proves that the preparation has the activity of inhibiting LTA4H for the first time. On the basis, the invention provides a hydrogel dosage form taking a prodrug SAHA-Ac of S-SAHA as an active loading drug, and proves that the hydrogel can inhibit LTA4H and down-regulate LTB4 through in-situ injection, so that the hydrogel has a new application in treating kidney inflammation.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of a nano-micelle-hydrogel preparation of an HDAC inhibitor with dual targets in the medicine for treating acute kidney injury. Background technique [0002] Acute kidney injury caused by renal ischemia-reperfusion accounts for about 80% of all kidney diseases, affecting about half a billion patients worldwide. Ischemia-reperfusion of the kidney will cause the overload of intracellular calcium ions, the increase of reactive oxygen species, the recovery of kidney pH, and then cause the inflammatory response and necrosis of cells. Today, the standard therapy for acute kidney injury is renin-angiotensin-aldosterone therapy, but the incidence of the disease has been on the rise, so there is an urgent need to find alternative innovative therapies. [0003] Acetylation is the most widespread and common modification of histones and plays a key role in ch...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K9/107A61K47/34A61K47/36A61K31/167A61P13/12A61P29/00
CPCA61K9/06A61K9/1075A61K47/34A61K47/36A61K31/167A61P13/12A61P29/00Y02A50/30
Inventor 韩京华沈杰卢亚欣叶开林新辉
Owner NANKAI UNIV
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