Pharmaceutical compositions
A composition and drug technology, applied in the field of treatment of movement disorders, can solve problems that have not been proved by experiments
Patent Information
- Authority / Receiving Office
- CN · China
- Current Assignee / Owner
- Publication Date
- 2020-01-14
Smart Images
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Abstract
Description
technical field
[0001] The present invention relates to (+)-β-dihydrotetrabenazine and (+)-α-dihydrotetrabenazine, (-)-α-dihydrotetrabenazine and / or (+)-β- Use of a composition of dihydrotetrabenazine for the treatment of movement disorders (Tourette's syndrome). Background technique
[0002] Movement disorders can generally be divided into two categories: hyperkinetic movement disorders and hypokinetic movement disorders. Hyperkinetic movement disorders are caused by increased muscle activity and can cause abnormal and / or excessive movements, including tremors, dystonia, chorea, tics, myoclonus, and stereotypic behavior.
[0003] Hyperkinetic movement disorders are often psychological in nature, arising from improper regulation of amine neurotransmitters in the basal ganglia.
[0004] Tourette syndrome is a specific hyperkinetic movement disorder, an inherited neurological disorder characterized by multiple physical and vocal tics. The tics are usually repetitive, but oc...
Examples
Embodiment 1
[0465] A study of the properties of dihydrotetrabenazine metabolites formed after administration of tetrabenazine to human subjects
[0466] Pharmacokinetic studies were performed to determine the plasma concentrations of + / - alpha and + / - beta dihydrotetrabenazine in healthy adult male volunteers following oral administration of 25 mg tablets once and multiple times daily under fasting conditions Level. The data are summarized below.
[0467] Table 1 summarizes the pharmacokinetic data obtained after a single oral dose of tetrabenazine at a dose level of 25 mg (fasted, N=08).
[0468] Table 1
[0469]
[0470] Table 2 summarizes the pharmacokinetic data obtained after multiple oral administrations of tetrabenazine at the 25 mg dose level (fasted, N=07).
[0471] Table 2
[0472]
[0473] The data shown in Tables 1 and 2 indicate that, in humans, the major metabolites are the (-)-α-dihydrotetrabenazine isomer, which is essentially active as a VMAT2 binder, and (+)-β ...
Embodiment 2
[0476] Study of the Effects of Compositions of (+)-α-Dihydrotetrabenazine and (-)-α-Dihydrotetrabenazine on Locomotor Activity and Stereotyped Behavior in Rats
[0477] The effects of a combination of (+)-α-dihydrotetrabenazine and (-)-α-dihydrotetrabenazine on locomotor activity and stereotyped behavior in rats were studied and compared with those of (+)- The effects of α-dihydrotetrabenazine and (-)-α-dihydrotetrabenazine isomers were compared.
[0478] Materials and Methods
[0479] Open Fields, Med Associates Inc.
[0480] Plastic syringe 1ml, Terumo. No.: SS-01T1
[0481] Animal gavage needle 15G, Instech Solomon, catalog number: 72-4446
[0482] Sartorius electronic balance A22101, Sartorius Weighting Technology, Germany
[0483] Needle 27G Terumo Myjector, 0.5ml, number: 8300010463
[0484] Plastic syringe 3ml, Soft-Ject, number: 8300005761
[0485] BD Microtainer K2EDTA tube number: 365975
[0486] Matrix 0.75ml, Alphanum tube, Thermo Scientific, number: 4274
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