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A large amount of the current literature dedicated to solid states of active pharmaceutical ingredients (APIs) pays special attention to polymorphism of flavonoids. Taxifolin (also known as dihydroquercetin) is an example of a typical flavonoid. Some new forms of taxifolin have been reported previously, however it is still unclear whether they represent polymorphic modifications. In this paper, we tried to answer the question about the taxifolin polymorphism. Taxifolin microtubes and taxifolin microspheres were synthesized from raw taxifolin API using several methods of crystal engineering. All forms were described with the help of spectral methods, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and thermal analysis (TA). SEM reveals that the morphology of the solid phase is very specific for each sample. Although XRPD patterns of raw taxifolin and microtubes look similar, their TA profiles differ significantly. At the same time, raw taxifolin and microspheres have nearly identical thermograms, while XRPD shows that the former is a crystalline and the latter is an amorphous substance. Only the use of complex analyses allowed us to put the puzzle together and to confirm the polymorphism of taxifolin. This article demonstrates that taxifolin microtubes are a pseudopolymorphic modification of raw taxifolin.

Taxifolin, also known as dihydroquercetin, is the major flavonoid in larch wood. It is well known as an antioxidant and a bioactive substance. Taxifolin as an active pharmaceutical ingredient is produced industrially in crystalline form during the processing of larch wood. Some information is available on nano- and microstructured particles of taxifolin. This paper reports on the generation of a new form of taxifolin as microtubes. These self-assembled tubes were obtained from raw taxifolin by crystal engineering with urea at ambient temperature and pressure. The parameters of temperature, pH value, molar ratio of taxifolin and urea, and time duration were optimized for yield enhancement of the microtubes. The water solubility and melting point of the new form of taxifolin were established. The microtubes were characterized by X-ray diffraction, X-ray powder diffraction, microscopy, mass spectrometry, 1 H NMR spectroscopy, UV spectroscopy and Fourier transform infrared spectroscopy methods. The experimental results demonstrate that the microtubes and raw taxifolin both exist in crystalline form with the same structure of the crystal unit. However, they are characterized by different morphological and physicochemical properties. Computer simulation was performed to explain the mechanism of the self-assembly process.

Dihydroquercetin effects on the tone of isolated segments of the portal vein of rats were studied. Dihydroquercetin did not modify the basal venous tone, but reduced the amplitude of contractions induced by KCl and norepinephrine hydrotartrate.

The clinical trials on 31 patients with arteriosclerosis and I-II stage discirculatory encephalopathy to assess an ability of Ascovertin to limit hemorheology abnormalities were carried out. In patients with discirculatory encephalopathy was a distinct increase in blood viscosity which was induced by disturbances of cell rheological factors: increase in aggregation of erythrocytes and decrease in their deformability were observed in comparison with indices in the group of healthy volunteers. No difference in plasma viscosity and fibrinogen was found. The treatment with Ascovertin in patients with discirculatory encephalopathy improved their attention, memory, mental performance, normalized sleep, releaved headache, decreased fatiquebility, led to the decrease in blood viscosity values, the reduction of pathological erythrocyte hyper aggregation and the improvement of erythrocyte deformability. We partly connect this clinical effect and hemorheology activity of Ascovertin with its antioxidant property--there was found impressive lipid peroxidation suppression. No significant changes in hemorheological and lipid peroxidation indices were observed in patients without Ascovertin., (Copyright 2004 IOS Press)

Peroral administration of 70 mg/kg ascovertin and 150 mg/kg Leuzea extract to rats with cerebral ischemia for 5 days prevented destructive changes and decrease in the density of synapses in the cerebral cortex. These preparations activated compensatory and reparative mechanisms underlying plasticity of the synaptic pool, which was realized through hypertrophy and destruction of synaptic contacts. Ascovertin possessed more pronounced cerebroprotective activity than Leuzea extract.

1. The major metabolites of ethacizin (ethyl 10-[3-diethylaminopropionyl]phenothiazine-2-carbamate) have been isolated from human urine by h.p.l.c. and identified by determination of u.v., i.r., n.m.r. and mass spectra and comparison with spectra of synthetic standard compounds. 2. The pathways of metabolism of ethacizin include N-de-ethylation, sulphoxidation, N-10 amide hydrolysis, aromatic hydroxylation and conjugation.