RESUMO
In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R2 = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f1 and similarity factor f2 were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.
RESUMO
<p><b>OBJECTIVE</b>To analyze and predict the trend in mortality rate of stomach cancer in twenty years in China.</p><p><b>METHODS</b>Stomach cancer mortality data collected from the China national survey over the period 1970s - 1990s for the cause of death were analyzed.</p><p><b>RESULTS</b>The adjusted mortality rate of stomach cancer in 1990s increased by 11.0% and 6.3% for males and females, respectively. The urban mortality in 1970s was slightly higher than the rural mortality, while in 1990s the rural mortality rate was about 60% higher than the urban mortality. In 1990s, the adjusted urban mortality rate decreased by 22.2% and 26.7% for males and females, respectively. In contrast, the rural mortality rate increased by 26.4% and 22.1% for males and females, respectively. The sex ratio of stomach cancer deaths in 1990s, both in cities and rural areas, was slightly greater than that in 1970s, being more marked in the latter areas. In 1990s, the mortality rate decreased in 12 provinces, accounting for 44% in both sexes (12/27), but the decrease was more marked for females than for males except in Kiangs province. In provinces where the increased rates ranked top six positions, the magnitude of increase in rates was higher in males than in females.</p><p><b>CONCLUSION</b>The overall mortality rates of stomach cancer in the past 20 years in China presented an increasing trend, despite there were upward and downward changes in 27 provinces and decrease in cities while increase in rural areas. Compared with other countries, the world-adjusted mortality rate of stomach cancer for both sexes in China ranks first. The increasing trend in stomach cancer mortality was seen in the older age groups (> 60 years) while a decreasing trend was seen in the younger age groups (30 - 59 years). Aging of the population could be an important factor responsible for the increase in mortality rates of stomach cancer in China.</p>