Application of 17-allylamine-17-demethoxygeldanamycin in preparation of medicine for treating epilepsy

A technology of methoxygeldanamycin and allylamine, which is applied in the field of 17-propenamine-17-desmethoxygeldanamycin to prepare medicines for the treatment of refractory epilepsy, and can solve the problem of no epilepsy reports, etc. question

Active Publication Date: 2015-08-19
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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  • Application of 17-allylamine-17-demethoxygeldanamycin in preparation of medicine for treating epilepsy
  • Application of 17-allylamine-17-demethoxygeldanamycin in preparation of medicine for treating epilepsy
  • Application of 17-allylamine-17-demethoxygeldanamycin in preparation of medicine for treating epilepsy

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Embodiment 1

[0037] The establishment of embodiment 1 epilepsy mouse model

[0038] 1. Drug injection method: Reagent:

[0039] DMSO: Dimethyl sulfoxide (Sigma, D4540-1L Lot#BCBK5723V)

[0040] 17-Allylamino-17-Demethoxygeldanamycin: 17AAG, [17-(Allylamino)-17-demethoxygeldanamycin], [17-(Allylamino)geldanamycin], [Tanespimycin] (LC Laboratories, A-688017- AAG, >99%,), Geldanamycin: (LC Laboratories, G-4500)

[0041] Preparation method:

[0042] (1) Dilute 17-propenylamine-17-desmethoxygeldanamycin to 50 mg / ml with DMSO, aliquot and store at -20°C in the dark.

[0043] (2) Injection concentration: 20 mg (diluted with DMSO, the final volume of each injection per mouse is 50 μl).

[0044] 2. Establishment method of model mice: We use unilateral hippocampus injection of kainate-induced medial temporal lobe epilepsy model mice, which is the classic and most commonly used model of refractory temporal lobe epilepsy. The first seizure lasting about 3 hours was induced by unilateral injecti...

Embodiment 2

[0045] Example 2 Effects of Drugs on the Expression Level of Mouse Hippocampus Glt1

[0046] 1. Experimental method

[0047] First, normal mice were intraperitoneally injected with 17-propenylamine-17-desmethoxygeldanamycin to determine the optimal injection dose and injection time. We selected a total of 5 experimental doses: 0mg / kg, 2mg / kg, 5mg / kg, 15mg / kg, 25mg / kg, and took mouse hippocampal protein at 24 hours, and found that when the injection concentration was 15mg / kg, monomer Glt1 The up-regulation of Glt1 is the most obvious, which is about 2.8 times that of the control. When the injection concentration is 25 mg / kg, although the expression level of monomeric Glt1 is decreased relative to the injection concentration of 15 mg / kg, the expression level of tetrameric Glt1 is increased. More obvious, about 2.0 times of the control (Figure 2). In the follow-up experiments, the injection concentration we chose was 20mg / kg.

[0048] For the selection of opt...

Embodiment 317

[0051] Example 31 Therapeutic Effect of 7-Allylamine-17-Demethoxygeldanamycin on Mouse Model Epilepsy

[0052] 1. Experimental method

[0053] After the baseline measurement, 17-propenylamine-17-desmethoxygeldanamycin or DMSO was administered. The dosing cycle is as follows: firstly, 2 rounds of 6-day dosing are carried out, in which the drug is injected continuously for the first five days, and no medicine is given on the sixth day. Then inject the drug every other day ( image 3 ). In this experiment, 13 mice were injected with 17-propenylamine-17-desmethoxygeldanamycin, and 8 mice were injected with DMSO. The results of EEG monitoring showed that the injection of DMSO itself did not affect the frequency of seizures before and after injection, while the injection of 17-propenylamine-17-desmethoxygeldanamycin significantly inhibited the number of seizures and effectively relieved the seizures ( Figure 4 , histogram, the left column of groups 1-21 is the baseline, the gro...

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Abstract

The invention relates to an application of 17-allylamine-17-demethoxygeldanamycin in preparation of medicine for treating epilepsy, wherein preferably, epilepsy is intractable epilepsy, and more preferably is temporal lobe epilepsy which is ineffectively treated by medicines. According to the invention, 17-allylamine-17-demethoxygeldanamycin is realized by up regulation of G1t1 protein in brain tissue. 17-allylamine-17-demethoxygeldanamycin is employed for effectively treating temporal lobe epilepsy which is ineffectively treated by medicines, simultaneously, other physiological states of a subject can not be influenced during a treatment period.

Description

technical field [0001] The present invention relates to the use of 17-propenylamine-17-desmethoxygeldanamycin in the preparation of drugs for treating epilepsy, in particular to the use of 17-propenylamine-17-desmethoxygeldanamycin in the preparation of refractory epilepsy Drug use in sexual epilepsy. Background technique [0002] Epilepsy is a group of syndromes characterized by recurrent, paroxysmal, transient, and usually stereotyped central nervous system dysfunction caused by different etiologies and caused by highly synchronized abnormal discharges of brain neurons. Epilepsy is one of the most common neurological diseases. According to statistics from the World Health Organization (WHO) and the International League Against Epilepsy (ILAE), about 50,000,000 people worldwide suffer from epilepsy, of which 85% are in developing countries. 2.4 million newly diagnosed patients. [0003] Epilepsy can be classified according to the site of onset and symptoms. 1. Site-relat...

Claims

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Application Information

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IPC IPC(8): A61K31/395A61P25/08
Inventor 许琪沙龙泽沈岩
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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