New application of geldanamycin and derivative thereof in treating and inhibiting posterior capsular opacification

A technology of geldanamycin and derivatives, applied in the field of medicine, can solve problems such as unseen cataract

Inactive Publication Date: 2018-02-27
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It has been reported that 17AAG has a good inhibitory effect on viruses and various tumors (see Joshi P, Maidji E, Stoddart CA. Inhibition of Heat Shock Protein 90 Prevents HIV Rebound. J BiolChem. 2016, 291 (19): 10332-46. and Pedersen KS, Kim GP, Foster NR et al. Phase II trial of gemcitabine and tanespimycin (17AAG) in metastatic pancreatic cancer: a Mayo Clinic Phase II Consortium study. Invest New Drugs Invest New Drugs. 2015,33(4):963-8. ), but there is no report about its use in post-cataract

Method used

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  • New application of geldanamycin and derivative thereof in treating and inhibiting posterior capsular opacification
  • New application of geldanamycin and derivative thereof in treating and inhibiting posterior capsular opacification
  • New application of geldanamycin and derivative thereof in treating and inhibiting posterior capsular opacification

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Inhibitory effect of 17-AAG on cell growth of human lens epithelial cell line HLE-B3.

[0037] Human lens epithelial cell line HLE-B3 cells are commonly used in post-cataract research. We selected HLE-B3 cell line to detect the inhibitory effect of 17AAG on the growth of lens epithelial cells. HLE-B3 cells by 6×10 3 Cells / well were seeded in 96-well culture plates, and the cell culture medium was DMEM containing 10% FBS. After culturing overnight, DMSO and 17AAG were added for treatment. In the 17AAG treatment group, 0.2 μl of 10 mM 17AAG was added to every 10 milliliters of culture medium to make a final concentration of 0.2 μM; in the control group, 0.2 μl of DMSO was added to every 10 milliliters of culture medium. There were 5 repetitions in each group, and they were treated for 0, 24, 48 and 72 hours, respectively. Cell proliferation was detected by MTS kit (Promega Company) combined with a microplate reader, and the detection wavelength was 490 nm.

[0038] T...

Embodiment 2

[0040] (1) 17-AAG inhibits the proliferation and migration of capsular lens epithelial cells cultured in vitro.

[0041] The in vitro mouse or rat lens capsular bag culture model is a commonly used in vitro model for studying post-cataract. We took Wistar rats (7-8 weeks, male or female, 200-250 g) as experimental animals, and after isoflurane inhalation anesthesia, the eyeballs of the rats were taken out, washed 3 times with PBS solution containing 5% penicillin and streptomycin, Remove the lens. Cool the autoclaved 2% cryogenic agar to 37 °C and pour into sterile molds. Place the prepared lens in the center of the agarose and suck out the excess agar to the equator of the lens. Cool the mold to room temperature until the agar solidifies. The anterior capsule of the lens was torn open with capsulorhexis forceps, and lactated Ringer's solution was injected into the capsule bag for water separation, so that the lens cortex and capsule were completely separated and protruded ...

Embodiment 3

[0052] Validation test of 17AAG promoting recovery of opaque lens capsular bag.

[0053] The lens capsule was cultured in vitro with DMEM containing 10% fetal bovine serum. On the third day, lens epithelial cells completely covered the lens capsule. The above crystal capsules were randomly divided into two groups: 17AAG treatment group and DMSO control group, with 3 crystal capsules in each group, and the liquid was changed every 7 days. The final concentration of 17AAG was 0.4 μmol / L, that is, 0.4 μl of 10 mM 17AAG was added to every 10 ml of culture medium. In the control group, 0.4 μl of DMSO was added to every 10 ml of culture medium. After adding the medicine, observe through an inverted microscope every day, and take pictures and record it for a total of 31 days. The result is as Figure 8 As shown, the lens capsular bag was cultured in vitro for 3 days, and the lens epithelial cells completely covered the posterior lens capsule, and then one group was added with 17AA...

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Abstract

The invention relates to new application of geldanamycin and a derivative thereof in treating and inhibiting posterior capsular opacification, belonging to the technical field of medicines. Experiments prove that a geldanamycin derivative 17AAG inhibits human lens epithelial cells from proliferating and induces lens epithelial cells to die; in an in vitro rat lens capsular bag cultivation model, 17AAG inhibits residual lens epithelial cells from proliferating, migrating and fiberizing in a lens posterior capsule greatly, induces cells with posterior capsule overgrown to die, and promotes turbid lens posterior capsule to recover transparency; in a rabbit intraocular lens replacement model, 17AAG can inhibit posterior capsular opacification. The geldanamycin and the derivative thereof inhibit posterior capsular opacification by inhibiting HSP90 molecular chaperone activity of lens cells, and have a therapeutical effect on the formed posterior capsular opacification at the same time. 17AAG has new application in treating posterior capsular opacification, and is a candidate medicine that 17AAG has development potential and can prevent and treat posterior capsular opacification.

Description

technical field [0001] The invention relates to a new application of geldanamycin and derivatives thereof for treating and inhibiting after cataract, and belongs to the technical field of medicine. Background technique [0002] Posterior cataract, also known as posterior capsule opacification (PCO), is the most common complication after cataract and intraocular lens replacement, resulting in further impairment of vision. Cataract is the world's first blinding eye disease. The application of intraocular lens replacement surgery to remove the cloudy lens is currently an effective means of treating cataract and restoring vision. However, after cataract surgery, the incidence rate of post-cataract in adults is 20-50%, and the incidence rate of children under 12 years old is 97% (see D.J.Apple, Q.Peng, N.Visessook, etal.Eradication of posterior capsule opacification:documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/395A61P27/12
Inventor 胡延忠李静崔秀坤任艳竹穆红梅杨争艳马远方李梦园
Owner HENAN UNIVERSITY
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