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Synapse formation agent

A synaptic and preparation technology, applied in the direction of medical preparations containing active ingredients, pharmaceutical formulas, bone/connective tissue cells, etc., can solve unproven problems such as spinal cord injuries, achieve advanced functional recovery, promote plasticity, and improve brain function. The effect of infarction

Pending Publication Date: 2018-12-21
SAPPORO MEDICAL UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] However, the above-mentioned mechanism of action is only speculation based on observed phenomena, and the mechanism of treating cerebral infarction and spinal cord injury through intravenous administration of MSC has not been confirmed.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1. Promotion of Synapse Formation and Plasticity in Rats with Cerebral Infarction

[0115] 1. Materials and methods

[0116] (1) Preparation of mesenchymal stem cells from rat bone marrow

[0117]Experiments were carried out in accordance with the animal experiment management regulations of Sapporo Medical University. According to previous reports, the bone marrow obtained from the femur of mature SD rats was diluted to 25 ml with Dulbecco's Modified Eagle Medium (DMEM), and 10% FBS and 2 mM l-glucose were added after heat inactivation. Aminoamide, 100U / ml penicillin, 0.1mg / ml streptomycin, in 5% CO 2 Incubate for 3 days at 37°C under atmosphere (Kim S. et al., Brain Res. 2006; 1123:27-33. Ukai R. et al., J. Neurotrauma. 2007; 24:508-520.). Cultured until it became confluent, the adherent cells were detached with trypsin-EDTA, and 1×10 4 cells / ml and subcultured three times to obtain mesenchymal stem cells (MSCs).

[0118] (2) Cerebral infarction model

[...

Embodiment 2

[0145] Embodiment 2. Therapeutic effect of vascular dementia rats

[0146] Stroke-prone spontaneously hypertensive rats (SHRSP (Stroke-prone spontaneously hypertensive rat)) develop dementia due to rupture of the BBB (blood-brain barrier) and lacunar infarction due to high blood pressure. Therefore, using SHRSP rats as a model of vascular dementia, the effect of MSC administration on dementia was verified using the following three methods: MWM (water maze test), NOR (new object recognition test), NOP (new object position test). NOR and NOP were implemented 1 week before transplantation, 1 week after transplantation, and 4 weeks after transplantation, and MWM was implemented at 5 weeks after transplantation.

[0147] 1. Materials and methods

[0148] (1) Vascular dementia model rats (SHRSP rats)

[0149] SHRSP rats were purchased from Hoshino Experimental Animal Breeding Institute. The rats are stroke-prone spontaneously hypertensive rats established by screening offspring ...

Embodiment 3

[0186] Embodiment 3. Therapeutic effect of patients with chronic cerebral infarction

[0187] MSCs were administered intravenously to patients with cerebral infarction in the chronic phase, and the improvement of higher functional levels was evaluated.

[0188] 1. Method

[0189] Bone marrow fluid was collected from the ilium of cerebral infarction patients under local anesthesia. Cells of interest are isolated from bone marrow fluid using a cell preparation facility (CPC), and cultured to about 10,000 times over about 2 weeks. Will be about 1x10 under GMP management 8 Each cell is enclosed in a bag of about 40ml to produce a cell preparation. The cell preparation was transplanted by intravenous administration over a period of 30 minutes to 1 hour.

[0190] Placebo was administered for 150 days in the first half (clinical trial I), MSCs were administered on the 150th day, and higher function was evaluated until the 250th day (clinical trial II).

[0191] (1) Aphasia index...

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Abstract

The present invention relates to a synapse formation accelerant and a brain plasticity accelerant that contain CD24-negative mesenchymal stem cells prepared from a patient's own bone marrow fluid, aswell as to treatment of dementia, chronic cerebral infarctions, chronic spinal cord injuries, mental disorders, or the like using the aforementioned synapse formation accelerant and brain plasticity accelerant.

Description

technical field [0001] [Related Application] [0002] Japanese Patent Application No. 2016-091286 (filed on April 28, 2016) and Japanese Patent Application No. 2016-091300 (filed on April 28, 2016) on which this application is based The contents described in the specification are included in the specification of this application. [technical field] [0003] The present invention relates to a synapse formation agent and a brain plasticity accelerator containing mesenchymal stem cells. More specifically, it relates to a synapse forming agent and a brain plasticity promoter comprising CD24-negative mesenchymal stem cells prepared from the patient's own bone marrow or blood. Background technique [0004] It is known that mesenchymal stem cells (Mesenchymal Stem Cells: MSCs) have protective effects on the brain (parenchyma and blood vessels). Using an experimental infarction model, it has been confirmed that administration of MSCs after cerebral infarction reduces infarct vol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/28A61P25/00A61P25/28
CPCA61K35/28A61P25/00C12N5/0663A61K9/0019
Inventor 本望修佐佐木祐典前泽理惠冈真一佐佐木优子中崎公仁山下敏彦
Owner SAPPORO MEDICAL UNIVERSITY
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