Dopa decarboxylase inhibitor compositions

A composition, levodopa technology, applied in the field of kits, can solve the problems of invasiveness and inconvenience

Active Publication Date: 2017-02-15
NEURODERM
View PDF5 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such treatments, especially intraduodenal, are extremely invasive and inconvenient

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Dopa decarboxylase inhibitor compositions
  • Dopa decarboxylase inhibitor compositions
  • Dopa decarboxylase inhibitor compositions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1. preparation preparation method

[0069] Formulations of levodopa (LD) and carbidopa (CD) can be prepared as follows:

[0070] Method #1 (L-Arg solution): Dissolve L-Arg and sodium bisulfite (Na-Bis) in water. The solution was added to the LD and CD powders. The mixture was stirred and heated at 75°C for 13 minutes until complete dissolution. The LD / CD solution was kept at room temperature (RT) for 10 minutes to cool.

[0071] Method #2 (all powders together): Weigh all powders (LD, CD and L-Arg) and add Na-Bis in water. The suspension was heated with stirring at 75°C for 13 minutes until complete dissolution. The LD / CD solution was kept at RT for 10 min to cool.

[0072] Method #3 (same as #2 without Na-Bis preheat): Weigh all powders (LD, CD and L-Arg) together and add water. The suspension was heated with stirring at 75°C for 13 minutes until complete dissolution. The LD / CD solution was kept at RT for 10 min to cool.

[0073] Method #4 (step prepar...

Embodiment 2

[0076] Example 2. Identification of major degradants in CD-containing formulations

[0077] A liquid formulation with levodopa, carbidopa and arginine was prepared using the method outlined in Example 1, and the carbidopa levodopa formulation was subjected to HPLC analysis using the Agilent 1100 system according to the APH Stability Indicating Analytical Method .

[0078] The HPLC system used here included the following components manufactured by Agilent: pump system (model G1311A), diode array detector (model G1315B), autosampler (model G1329A), degasser (model G1379A), thermostat (model G1330B), thermostat column compartment (model G1316A). The column used is a new Synergi 4μFusion-RP 80A, 250×4.6mm

[0079] HPLC working conditions : wavelength: 280nm; flow rate: 1.0ml / min; injection volume: 10μl; column temperature: 30°C; thermostat temperature: 4°C; stop time: 27 minutes; pressure: 105bar.

[0080] mobile phase preparation : solvent A: acetonitrile, solvent B: 20 ...

Embodiment 3

[0093] Example 3. Effect of ascorbic acid with or without EDTA on the stability of LD / CD formulations

[0094] Liquid formulations were prepared by weighing all powders (LD, CD, EDTA, ascorbic acid and L-Arg) and adding water preheated to 73±3°C. Place the suspension in a water bath at 73±3°C and stir for 10 minutes until completely dissolved. The LD / CD solution was kept at RT for 10 min to cool. The solution was divided into glass vials and kept at +25°C and -20°C for the indicated times. Place frozen vials at RT until completely thawed prior to analysis. The formulations were then mixed and analyzed for stability. The effect of ascorbic acid with or without EDTA on the stability of LD / CD formulations was measured by HPLC. The levels of degradants presented in Table 4 and Table 5 (as a percentage of the initial CD amount) represent the level of stability of the LD / CD formulations and indicate that EDTA has no significant effect on the stability of the LD / CD formulations. ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The present invention provides highly stable carbidopa-based pharmaceutical compositions comprising an antioxidant combination consisting of ascorbic acid and at least one additional antioxidant, wherein said combination strongly inhibits carbidopa degradation. These compositions may further comprise levodopa and / or one or both of arginine and meglumine, and are beneficial in treatment of a disease, disorder or condition associated with loss of dopamine or dopaminergic neurons, e.g., Parkinson's disease.

Description

technical field [0001] The present invention provides pharmaceutical compositions of carbidopa and optionally levodopa, containing safe and tolerated concentrations of hydrazine, as well as methods of use and kits comprising them. Background technique [0002] Parkinson's disease is a degenerative condition characterized by decreased concentrations of the neurotransmitter dopamine in the brain. Levodopa (L-dopa or L-3,4-dihydroxyphenylalanine), the immediate metabolic precursor of dopamine, unlike dopamine, is able to cross the blood-brain barrier and is most commonly used to restore brain concentration of dopamine in . For the past 40 years, levodopa has been the most effective therapy for Parkinson's disease. [0003] However, even with the best current standard of care, levodopa has a short half-life in plasma, resulting in pulsatile dopamine stimulation. Thus, for some patients long-term treatment is complicated by motor fluctuations and dyskinesia, which can indicate...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K47/22A61K47/20A61K31/198A61P25/16
CPCA61K31/198A61K47/183A61K47/22A61K9/0014A61K31/133A61K9/0019A61K47/20A61P25/16A61K47/26
Inventor 奥伦·亚柯比-泽维
Owner NEURODERM
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products