Application of homopsyllogen in preparation of catechol drug synergist and pharmaceutical composition containing homopsyllogen
A technology of high psyllium and composition, which is applied in the directions of drug combination, active ingredients of heterocyclic compounds, pharmaceutical formulations, etc., to achieve the effects of improving solubility, prolonging metabolic half-life in vivo, and eliminating synthesis steps
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Embodiment 1
[0022] Example 1. Oral acute toxicity assessment of mice with high psyllogen
[0023] Select Kunming mice (purchased from Experimental Animal Center of Dalian Medical University), half male and half female, weighing 19-22 g. The mice were divided into random groups, 20 in each group, half male and half male. Homopsyllogen was suspended in 0.5% CMC-Na at a concentration of 1 g / L. The experimental groups include different dosage groups of high psyllium (0.2-2 g / kg) and 0.5% CMC-Na blank control group. The behavioral state of the mice after administration was continuously observed until 14 days, and on the 14th day, the mice in different administration groups were grossly dissected and the internal organs were observed. There were only 3 cases of death in the mice in the administration group of the maximum dose group (2g / kg), and no cases of death in other dose groups. An autopsy of the deceased individual did not reveal any obvious lesions in major organs such as liver and ki...
Embodiment 2
[0024] Example 2. Determination of the inhibitory activity of homopsyllogen compounds on human COMT enzymes
[0025] Using the L-dopa methylation reaction as a probe reaction, with the help of human liver cell plasma in vitro incubation system, the IC50 of high psyllogen compounds on the inhibition of COMT enzyme was determined. The specific experimental procedure is as follows:
[0026] (1) Add MgCl to 200 μl in vitro metabolic reaction system 2 , dithiothreitol, substrate L-dopa, human liver cell plasma protein concentration of 1mg / ml, high psyllidine (final concentrations were 2.5, 5, 10, 20, 50, 75, 100nM) and Tris- HCl buffer solution; a blank control group (without adding psyllogen) was also set up.
[0027] (2) Add 0.2mMS-adenosylmethionine to the reaction system to initiate the reaction; after reacting at 37°C for 30 minutes, add 200μl of acetonitrile and shake vigorously to terminate the reaction; incubate the cofactors, L-dopa And the adding amount of high psyllium...
Embodiment 3
[0033] Example 3. Whole Pharmacokinetic Study of Rats Combined with Homopsyllogen and L-dopa
[0034] 18 Wistar rats, half male and half female, were randomly divided into groups according to body weight (180-220g), and 6 rats / group were given oral administration of L-dopa alone and simultaneous oral administration of high psyllium (50mg / kg) and L-dopa (50mg / kg). ) overall pharmacokinetic study, and compared with the positive control (tolcapone) on the pharmacokinetics of L-dopa. About 0.5ml of rat plasma samples were collected before administration and at 5, 10, 15, 30, 45, 60, 90, 120, 180, and 240 minutes after administration, and placed in a 1.5ml apex of pre-heparinized In a brown centrifuge tube, centrifuge at 4000×g for 10 minutes, separate the plasma, add an equal volume of methanol to precipitate the protein and centrifuge at a high speed (20,000×g), remove the supernatant and store in a -80°C refrigerator for testing. UFLC-ESI-MS was used to measure the blood concen...
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