Application of phthalide compounds

A kind of compound, the technology of phthalide, applied in the application field of phthalide compound

Active Publication Date: 2018-10-09
EVERFRONT BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there is still no effective treatment for the related diseases caused by the degeneration of Purkinje cells. At most, physical therapy and respiratory system care can be used to reduce the incidence of complications and slow down the speed of disease progression.

Method used

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  • Application of phthalide compounds
  • Application of phthalide compounds
  • Application of phthalide compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] [Example 1] In vitro cell test

[0039] cell transfection

[0040] This experiment tested the effect of butylenephthalide and 3-butylene-4,5-dihydrophthalide on the expression level of SCA3 protein. First, pEGFP-C1-Ataxin3Q84 (i.e., the plastid of the Ataxin gene with an abnormal number of CAG repeats (84Q)) or pEGFP-C1-Ataxin3Q28 plastid (i.e., the plastid with the normal number of CAG repeats (28Q)) containing green fluorescent protein The plastid of the Ataxin gene) (purchased from Addgene Company, the U.S.), through the transfection reagent ( 2000Transfection Reagent, Invitrogen TM ) into human embryonic kidney cells (Human embryonickidney, HEK) 293T ((Bioresource Collection and Research Center, Taiwan) or neural stem cells (Neural stem cell, NSC). Cells were cultured in 10% fetal bovine serum (Gibco) DMEM medium (Dulbecco's modified Eagle's medium, Thermo), in 5% CO 2 in a 37°C incubator. After that, butylenephthalide (A10353, purchased from Alfa Aesar, USA; ...

Embodiment 2

[0042] [Example 2] Zebrafish in vivo test

[0043] (1) Test safe dosage

[0044] In this experiment, zebrafish was used as the animal model. The zebrafish strain used in the experimental group was Tg(HuC:GFP), which is characterized by primary sensory neurons (Rohon-Beard cells) that can produce fluorescence, so it is convenient for observation. Wild-type strains were used, and all fish species were provided by TZCAS (Taiwan Zebrafish Core Facility at Academia Sinica, Taiwan) and TZCF (Taiwan Zebrafish Core Facility at Academia Sinica, Taiwan). First, to test the toxicity of butylenephthalide to zebrafish, inject different doses of butylenephthalide into zebrafish, culture them at 28.5°C, and observe their survival rate after 48 hours.

[0045] The result is as figure 2 As shown, the survival rate of wild-type zebrafish was 100%, while the survival rate of zebrafish injected with 500 mg / kg butylenephthalide was about 50%, and the survival rate of zebrafish injected with 250...

Embodiment 3

[0052] [Example 3] Mouse in vivo test

[0053] In this experiment, MJD84.2 gene-transformed mice (ie, mice transfected with human 84CAG repeated ATXN3 gene, referred to as SCA3 mice) were used for the experiment. MJD84.2 transgenic mice are animal models for the study of spinocerebellar atrophy. These mice will have abnormal gait within 4 weeks after birth, and then begin to show mild tremor and moderate mobility. Decreased, abnormal contraction of front / hind limbs (about 24 weeks old), and weakness on the ground.

[0054] (1) Treatment of MJD84.2 gene transfected mice

[0055] Two-week-old MJD84.2 gene transgenic mice were randomly divided into 5 groups, 6 mice in each group, and were treated for 2 weeks under the following conditions: (1) untreated; (2) fed with olive oil (i.e. , only fed adjuvant); (3) fed butylenephthalide 100 mg / kg / day divided into two feedings (bid); (4) fed butylenephthalide 500 mg / kg / day divided into two feedings (bid) ; (5) Feed 3-butylene-4,5-dihy...

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Abstract

A method for treating and / or delaying the degeneration of Purkinje cells in a subject is provided. The method comprises administering to a subject in need thereof a therapeutically effective amount of a medicament, wherein the medicament comprises a phthalide selected from the group consisting of n-butylidenephthalide (BP), a metabolic precursor of BP, a pharmaceutically acceptable salt of a metabolic precursor of BP, a pharmaceutically acceptable ester of a metabolic precursor of BP, and combinations thereof.

Description

technical field [0001] The present invention relates to the application of phthalide compound (phthalide), especially to the application of using phthalide compound to treat and / or delay the degeneration of Purkinje cells, especially to treat spinal cerebellar atrophy and Alzheimer's disease Syndrome, at least one of Parkinson's disease and / or delaying its onset. Background technique [0002] Neurons, also known as nerve cells, are one of the structural and functional units of the nervous system of organisms. They can transmit information with other cells by means of chemical signals and electrical signals. They have various shapes and sizes, with a diameter of From about 4 microns to about 100 microns, the structure can be roughly divided into three parts: the cell body, dendrites, and axons. The dendrites can bring information into the cell body, and the axon can carry information Emitted from the cell body. [0003] Purkinje cells are neurons in the cerebellum responsib...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/365A61P25/00A61P25/28A61P25/16
CPCA61K31/365A61P25/00A61P25/16A61P25/28
Inventor 林欣荣韩鸿志邱紫文吴政翰阎思尹
Owner EVERFRONT BIOTECH
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