Application of butylphthalide and derivatives thereof in preparation of medicines for preventing and treating ALS

A technology of butylphthalide and racemic butylphthalide, which is applied in the field of medicine to achieve the effect of improving the amplitude of action potential and the number of motor units, having a good application prospect and reducing degenerative diseases

Active Publication Date: 2012-04-04
SHIJIAZHUANG PHARMA GRP NBP PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

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  • Application of butylphthalide and derivatives thereof in preparation of medicines for preventing and treating ALS
  • Application of butylphthalide and derivatives thereof in preparation of medicines for preventing and treating ALS
  • Application of butylphthalide and derivatives thereof in preparation of medicines for preventing and treating ALS

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1: Identification of ALS transgenic mice

[0060] The ALS transgenic mouse that is widely used in clinical and basic research is SOD1-G93A mouse, which carries the SOD1 gene that expresses the missense mutation of human G93A (the 93rd glycine in the amino acid chain is replaced by alanine), which can simulate the chronic progression of ALS The course of the disease and some pathological and biochemical manifestations. The main characteristics of SOD1-G93A mice: about 3-4 months of hindlimb weakness, hindlimb tremor and abduction weakness when the tail is suspended, after 2 weeks, one or two limbs of the mouse are paralyzed, and the hair gradually appears rough and thin, 5 Months later, he was unable to exercise and finally died of respiratory failure.

[0061] The ALS transgenic mouse of the present invention (B6SJL-TgN[SOD1-G93A]1Gur, number 002726) was purchased from Jackson Laboratory (Barharbor, ME, U.S.A).

[0062] 1.1 Identification of offspring mice

...

Embodiment 2

[0071] Example 2: Observing the effects of racemic butylphthalide on the onset time, survival period and motor function of ALS mice

[0072] The mental state, disease progression and survival of all SOD1-G93A transgenic mice were observed every day. Judgment of the onset: Observation of limb tremor and / or limb weakness for 2 consecutive days was judged as the onset of death. Time of death: the rat was placed in the supine position, and the death was judged if the rat could not turn over to the prone position within 30 seconds.

[0073] Rotarod Test: The rotarod test assesses motor coordination, strength, and balance. The experimental mice were placed on a rotarod instrument with a diameter of 3.5cm, and the speed was adjusted to 16rpm. The longest latency period for falling was recorded, with 180 seconds as the cut-off value. If it exceeded 180 seconds, it was recorded as 180 seconds, and if it was less than 180 seconds, it was recorded as the actual time. The evaluation of t...

Embodiment 3

[0078] Example 3: Electrophysiological detection of ALS transgenic mice

[0079] Spontaneous potential: the experimental rat was anesthetized with 10% chloral hydrate, and the concentric needle electrode was inserted into the gastrocnemius muscle belly of the hind limb, and observed whether there was a fibrillation potential and (or) a positive sharp wave.

[0080] Recording of Compound Muscle Action Potential (CMAP): Rats were anesthetized with 10% chloral hydrate, the lumbar paraspinal sciatic nerve was stimulated, and the recording electrode was inserted into the gastrocnemius muscle belly of the hind limb. Give super strong stimulation, get CMAP and record, measure peak-to-peak value to represent CMAP amplitude, and record distal motor latency (DML).

[0081] Motor unit number (MUNE) evaluation: Referring to the principle of "statistical methods and techniques", the experimental mice were anesthetized with 10% chloral hydrate, the lumbar paraspinal sciatic nerve was stimul...

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Abstract

The invention which relates to the medicinal field discloses an application of butylphthalide and derivatives thereof in the preparation of medicines for preventing and treating ALS (amyotrophic lateral sclerosis). Butylphthalide and the derivatives, which can delay the disease time of an SOD1-G93A transgenic mouse, prolong the lifetime of the mouse, reduce the degenerative change of spinal motorneurons, obviously increase the survival number of spinal anterior horn motor neurons of the mouse, reduce the electrophysiological abnormality of the transgenic mouse, obviously improve the action potential amplitude and the motion unit number of compound muscles, substantially inhibit the activation of astrocytes and microglial cells in the spinal cord of the mouse, and obviously reduce the expression level of iNOS and NF-kappaBp65, have good application prospects in the prevention and the treatment of the ALS.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of butylphthalide and derivatives thereof in the preparation of medicines for preventing and treating ALS. Background technique [0002] Amyotrophic lateral sclerosis (ALS), also known as Charcot's disease or Lou Gehrig's disease, is a fatal motor neuron degenerative disease. The global incidence rate of ALS is 5-7 / 100,000, the age of onset is 40-60 years old, and the male-to-female incidence ratio is 1.4-2.5:1. The main clinical manifestations are muscle weakness, muscle fasciculation, and muscle atrophy. The disease affects the throat muscles, causing difficulty in speaking and swallowing; it can also affect the respiratory muscles, leading to dyspnea and death. The disease starts insidiously and progresses gradually. The average survival period is about 3 to 5 years, and most of them die from respiratory failure in the end, which brings a heavy burden to the country, s...

Claims

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Application Information

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IPC IPC(8): A61K31/365A61K31/5375A61K31/4453A61K31/235A61K31/192A61P25/00A61P21/00A61P21/04
Inventor 崔丽英冯新红彭英刘明生王建明管宇宙曹菊林牛锋郭海波黄印
Owner SHIJIAZHUANG PHARMA GRP NBP PHARMA CO LTD
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