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Application of phthalide compound

A compound, phthalide technology, applied in the application field of phthalide compounds, can solve the problem of no significant curative effect on motor neuron degenerative diseases

Active Publication Date: 2014-09-17
HAWKING BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, previous studies have also shown that stem cell therapy has no significant effect on motor neuron degenerative diseases, or can only provide relatively limited effects, for example: only prolonging the lifespan of mice with amyotrophic lateral sclerosis To about 140 days (see Garbuzova-Davis et al., Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose, 2008)

Method used

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  • Application of phthalide compound
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] [Example 1] Metabolites of Butylenephthalide

[0060] It is known that the drug metabolism pathways of drugs in the liver of living organisms can be mainly divided into first-order (phase I) metabolism and second-order (phase II) metabolism. The first-order metabolism is mainly the oxidation-reduction reaction or hydrolysis reaction of the drug , the second-order metabolism is mainly carried out by the cytochrome P450 monooxygenase (cytochrome P450 (CYP450) monooxygenase) system for metabolic reactions. In this example, the mixed reaction of butylenephthalide with liver microsomes or cryopreserved liver cells (cryopreserved hepatocytes) in vitro is used to simulate the process of butylenephthalide in the liver of a living body. The first-order metabolism and second-order metabolism of phthalide, and the products in the solution after the reaction were analyzed by liquid chromatography tandem mass spectrometry (LC-MS / MS) to confirm the metabolites and metabolic profiles of...

Embodiment 2

[0074] [Example 2] In vivo test of survival rate of transgenic mice

[0075] It is known that about 20% of the patients with amyotrophic lateral sclerosis will have the gene mutation of copper / zinc superoxide dismutase (SODl), among which the G93A mutation site is the most. The mutant human SOD1-G93A gene-transformed mouse (herein referred to as "SOD1-G93A gene-transformed mouse") can be used clinically for the study of amyotrophic lateral sclerosis because of its similar disease characteristics to humans. As an animal model of the disease, the SOD1-G93A gene transfected mice will start to develop symptoms at about the 90th ± 5th day after birth, and die at about the 125th ± 5th day after birth.

[0076] In this example, the above-mentioned SOD1-G93A gene transfected mice were used as research objects for in vivo experiments. The experiments were divided into the following five groups: (A) control group (no drug administration); (B) Relidex Experimental group: On the 60th day...

Embodiment 3

[0081] [Example 3] In vivo test of atrophic lateral sclerosis

[0082]In this example, SOD1-G93A gene transfected mice were used as the subjects of in vivo experiments. The 60-day-old SOD1-G93A gene transgenic mice were randomly divided into the following five groups: (A) control group (no drug administration); (B) Relidex experimental group: born in SOD1-G93A gene transgenic mice On the 60th day after that, the regular intraperitoneal injection of Rilide was started, once a day, and each dose was 16 mg / kg body weight; (C) Butylidenephthalide (n-butylidenephthalide: containing Z-BP95%+E-BP5%) experimental group (BP500mg / kg / qd): On the 60th day after birth, the SOD1-G93A gene transfected mice were orally administered with butylenephthalide (purchased from Jingming Chemical), once a day, each dose of 500 mg / kg body weight ; (D) Butylidenephthalide (n-butylidenephthalide: containing Z-BP95%+E-BP5%) experimental group (BP250mg / kg / bid): start timing on the 60th day after birth of ...

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Abstract

An application of a phthalide compound in preparing a medicament. The medicament is specially used for promoting a stem cell to secrete one of the following items: telomerase, a neurotrophic factor (brain-derived neurotrophic factor, BDNF), a stem cell chemotactic factor (stromal cell-derived factor-1, SDF1), a stem cell chemotactic factor receptor (CXC chemokine receptor 4, CXCR4), and an immunoregulatory factor; a kit comprising a phthalide compound and a stem cell is also provided.

Description

technical field [0001] The present invention relates to the application of phthalide compounds (phthalide), especially to the use of phthalide compounds in the preparation of promoting stem cells to secrete telomerase (telomerase), neurotrophic factor (brain-derived neurotrophic factor, BDNF), stem cell chemokine (stromal cell -derived factor-1, SDF1), stem cell chemokine receptor (CXC chemokine receptor4, CXCR4), and the application of at least one of immunomodulatory factors, especially for the preparation of drugs for the treatment of motor neuron degenerative diseases and / or the application of drugs that delay 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 to other cells through chemical signals and electrical signals. They have various shapes and sizes, with a diameter of From about 4 microns to about 100 microns, the structur...

Claims

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Application Information

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IPC IPC(8): A61K31/365A61K31/192A61K31/198A61K31/7024A61K31/7048A61K38/06A61K35/12A61K35/28A61K35/14A61K35/50A61K35/44A61P25/00A61P21/04A61P25/28A61P21/00
Inventor 林欣荣韩鸿志邱紫文薛国伟黄茂轩
Owner HAWKING BIOLOGICAL TECH
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