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Application of compound to preparation of drug for treating Parkinson's disease

A Parkinson's disease, compound technology, applied in the field of pharmaceuticals, can solve the problems of reduced buffering capacity of exogenous dopamine drugs, loss of dopamine production ability, etc.

Active Publication Date: 2016-11-23
SHANGHAI TONGJI HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, with the continuous development of PD and continuous levodopa administration, the ability of the remaining dopaminergic neurons to produce dopamine is lost, and the buffering ability of exogenous dopamine drugs is reduced.

Method used

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  • Application of compound to preparation of drug for treating Parkinson's disease
  • Application of compound to preparation of drug for treating Parkinson's disease
  • Application of compound to preparation of drug for treating Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 Pharmacodynamic experiment of AM1241 in treating Parkinson's disease in mice

[0032] First, the classical MPTP method was used to establish a subacute model of PD in C57 mice: MPTP (mg) required for each mouse: mouse body weight (0.02g) × 30mg / kg (MPTP) × administration time (5d). After intraperitoneal injection for 5 consecutive days (dosing at a fixed time every day), the mice were left for 5 days to evaporate the remaining MPTP in the cage, and the mouse rotarod experiment analysis showed that the success rate of modeling was as high as 85%.

[0033] In the second step, the successfully modeled PD mice were divided into random groups, 6 in each group, administered with PBS and AM1241 (AM1241 used in this embodiment, purchased from Selleck China), and a normal control group was set at the same time. The dose of AM1241 was (1.5mg / kg / d), administered by intraperitoneal injection, and administered continuously for 2 weeks. During the experiment, the mice were...

Embodiment 2

[0046] The preparation experiment of the solid lipid nanoparticle dosage form of embodiment 2 AM1241

[0047] (1) Synthesis steps of SLN-AM1241:

[0048] (1) Weigh 0.25g surfactant Myrj59, dissolve in 30ml double distilled water to form water phase;

[0049] (2) Fix the three-neck flask in a constant temperature magnetic stirring water bath, and add the prepared water phase when the water temperature rises to 75°C;

[0050] (3) Weigh 0.25g of stearic acid, 0.1g of lecithin, 20mg of AM1241, mix and dissolve in 10ml of chloroform, oscillate and ultrasonically mix, and inject into the water phase at a constant speed with a 6# syringe;

[0051] (4) Stir at 1000rpm for about 0.5h. When the mixed solution is milky, add 10ml of cooled double distilled water, and place the three-neck flask on ice and continue to stir for 2h;

[0052] (5) After stirring, transfer the sample to a centrifuge tube, wash twice with double distilled water at 4°C and 20,000rpm; freeze-dry the washed sample...

Embodiment 3

[0055] Example 3 Solid Lipid Nanoparticles (SLN-AM1241) of AM1241 Improves Brain Targeting Experiment

[0056] (1) Taking C57 mice with successful PD modeling as the experimental subjects, they were divided into groups and given AM1241 and SLN-AM1241 at a concentration of 1.5 mg / kg, and administered intraperitoneally for 14 consecutive days;

[0057] (2) The mice were killed on the 15th day, and each organ (heart, liver, spleen, lung, brain) was taken out respectively;

[0058] (3) Use tissue scissors or a scalpel to quickly separate the cleaned tissue into suitable small pieces, such as 1cm^3;

[0059] (4) Usually add 3 to 5 times the volume of pre-cooled homogenization buffer per volume of wet weight tissue to the homogenization container;

[0060] (5) Homogenize blade-type tissue breaker and incision-type tissue homogenizer at a speed of 1000-3000 rpm, high-speed homogenate 3 times, 20-30 seconds each time, pause for a few seconds between times, and operate on ice;

[006...

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Abstract

The invention relates to the technical field of pharmaceutics and discloses the application of the compound AM-1241, namely (R,S)-3-(2-iodo-5-nitrobenzene formyl)-1-(1-methyl-2-piperidinyl methyl)-1H-indol to preparation of a drug for treating Parkinson's disease. According to the compound, a cannabinoid receptor CB2 is used as the effective target spot of Parkinson's disease treatment, and symptoms of Parkinson's disease can be relieved greatly; furthermore, a molecular mechanism shows that CB2 expression of substantia nigra and hippocampus are activated, the occurrence rate of neuronal apoptosis is reduced, and a remarkable neuroprotective effect is realized; besides, by preparing the compound into solid lipid nanoparticle preparations for administration, drug absorption rate and brain-targeting effect can be improved, so that Parkinson's disease treatment effect is further improved. It is expected to prepare the drug for treating Parkinson's disease with the compound as the effective constituent, and the drug can become the substitution of existing levodopa drugs.

Description

technical field [0001] The present invention relates to the field of pharmaceutical technology, in particular to compound AM-1241, i.e. (R,S)-3-(2-iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinyl) Base)-1H-indole, the application in the preparation of the medicine for the treatment of Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is a common middle-aged and elderly neurodegenerative disease, clinically manifested as resting tremor, increased muscle tone, and bradykinesia. Although PD has been studied for nearly 200 years, so far, due to the unclear pathogenesis of PD, the existing medical technology cannot cure PD. [0003] Pathologically, the degeneration of dopamine (DA) neurons in the substantia nigra reticular zone and the decrease of striatal DA levels can be seen in the pathology of PD. Therefore, L-dopa (L-dopa) replacement therapy is the most widely used and most effective method. However, with the continuous development of PD and contin...

Claims

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Application Information

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IPC IPC(8): A61K31/454A61K9/16A61K9/127A61P25/16
Inventor 朱融融靳令经
Owner SHANGHAI TONGJI HOSPITAL
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