Methods and compositions for reducing neurodegeneration in amyotrophic lateral sclerosis

A technology for lateral sclerosis, a neurodegenerative disease, applied in the field of composition of at least one symptom, able to solve the problem that no effective treatment exists

Inactive Publication Date: 2007-10-03
柳署弘
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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  • Methods and compositions for reducing neurodegeneration in amyotrophic lateral sclerosis
  • Methods and compositions for reducing neurodegeneration in amyotrophic lateral sclerosis
  • Methods and compositions for reducing neurodegeneration in amyotrophic lateral sclerosis

Examples

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Effect test

Embodiment 1

[0076] Embodiment 1: the preparation of bile acid solution

[0077] A stock solution of bile acids was first prepared by dissolving UDCA (60 g) in 500 mL NaOH (6.7 g) solution. Next, 375 g of maltodextrin were added to the resulting clear solution with vigorous stirring in stages. The pH was then adjusted to 7.0-7.2 by dropwise addition of HCl and high-throughput ultrasound (750 W, 20 kHz). Then adjust the volume to 1.0 L with distilled water for injection. Finally, the resulting clear solution was filtered and sterilized under aseptic conditions with a 0.22 μGP express plus filter. (This filtration is important for sterilization, but not for removal of particulate matter since the solution is already clear). Dilutions of this solution at the desired concentration of UDCA are prepared according to standard pharmacy practice.

Embodiment 2

[0078] Embodiment 2: the preparation of bile acid solution

[0079] A stock solution of bile acids was first prepared by dissolving UDCA (25 g) in 400 mL NaOH (2.7 g) solution. Next, 745 g of maltodextrin were added to the resulting clear solution with vigorous stirring in stages. To the resulting solution was added 100 mL of a preservation solution containing 0.95 g of methylparaben and 0.3 g of sodium bisulfite, followed by stirring. The volume was then adjusted to 1.0 L with pharmaceutical grade water. Finally, filter the resulting clear solution with a suitable filter device. (This filtration was not done to remove particulate matter since the solution was already clear). Dilutions of this solution at the desired concentration of UDCA are prepared according to standard pharmacy practice.

Embodiment 3

[0080] Embodiment 3: animal test

[0081] Transgenic rats; the transgenic animals used in this example are heterozygous hSOD1 carrying a glycine 93-alanine mutation (G93A). This line exhibited B6SJL-TgN(SOD1-G93A)1Gur (The Jackson Lab., Bar Harbor, ME, USA) containing a reduced copy number of hSOD1, purchased from Jackson Laboratories. Transgenic mice that overexpress the human SOD1 gene containing mutations identified in ALS patients develop adult-onset, progressive motor deterioration. These transgenic mice are considered a model of the disease and have been used to test a number of strategies to delay disease progression and mortality.

[0082] To evaluate the potential benefit of the present invention on ALS, G93A transgenic mice were orally administered twice weekly with 240 mg / kg of the present solution dissolved in UDCA, starting at 70 days of age and continuing until death.

[0083] Life expectancy and its outcomes; Figure 1 shows the mean life expectancy of control ...

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Abstract

The present disclosure is related to clear aqueous solutions of one or more bile acids and either an aqueous soluble starch conversion product or a non-starch polysaccharide. Solutions of the disclosure may be administered to a subject in conjunction with a pharmaceutical compound having a therapeutic effect in subjects with a neurodegenerative disease and/or a motor neuron disease. In some embodiments, the disease is amyotrophic lateral sclerosis.

Description

technical field [0001] The present disclosure relates to compositions and methods for ameliorating or treating at least one symptom of a neurodegenerative process or disease. Background technique [0002] At any given time, as many as 30,000 Americans suffer from the almost always fatal amyotrophic lateral sclerosis (ALS). ALS, also known as Lou Gehrig's disease, is a progressive neurodegenerative disease that attacks motor neurons in the brain and spinal cord and causes muscle weakness and atrophy. Early symptoms include loss of dexterity and gait. As the disease progresses, patients become paralyzed and require respiratory support. After diagnosis, the life expectancy of ALS patients is usually 3 to 5 years, and the leading cause of death is loss of respiratory function. [0003] The etiology of ALS is only partially understood. Familial (inherited) cases account for only about 5%-10% of all ALS patients. In this subgroup of ALS patients, one in five carries the only ...

Claims

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Application Information

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IPC IPC(8): A61K31/575A61P25/16A61K47/36A61P25/28A61K9/00
CPCY02A50/30
Inventor 柳署弘
Owner 柳署弘
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