مقالههای Ahmad Fazeli
توجه: محتویات این صفحه به صورت خودکار پردازش شده و مقالههای نویسندگانی با تشابه اسمی، همگی در بخش یکسان نمایش داده میشوند.
۱A Study on the Mechanism of Aggregation of Therapeutic Reteplase Protein by Using the Monomer–Loss Model
اطلاعات انتشار: Journal of Applied Biotechnology Reports، دوم،شماره۱، Winter ۲۰۱۵، سال ۰
تعداد صفحات: ۷
Aggregation of pharmaceutical proteins reduces the efficiency and increases the cost of production. It can also lead to the reduced efficacy of drug or cause side effects on the patient’s body. Investigating how to create them plays an important role to find agents that prevents the aggregation. This study was allocated for understanding the mechanism of formation of the reteplase protein using thermal stimulation. Aggregation was studied by ultraviolet spectrometry, and observation at 4, 25, 50 and 70°C, the concentration of protein monomer was measured by using a spectrum of 360 nm and 280 nm. At 4°C, there was no significant change in monomer concentration for a month. By increasing the temperature to 25˚C, aggregation process was slow, but at 70°C, the reaction was carried out at a rapid rate less than 2 hours. In order to investigate the mechanism of reteplase aggregation, some kinetics that was presented in of monomer–loss models were used. Experimental data was fitted in three “pre balance core”, “self–catalytic” and “slow start” models using MATLAB. The best fit was obtained using optimization methods. Best fit for self–catalytic model is (R2> 0.98). For other two models (R2 0.9) occurred. The best fit for the pre balance core and a slow start model was occurred in n = 2. These results could indicate that the core is formed by connecting two reteplase monomers together. The reaction rate constants were calculated too. The results showed that increasing the temperature increases the reaction rate constant. With increasing temperature from 25 ˚C up to 70˚C, both of K1 and K2 increased from 4.7±0.1*10–11K1(min–1) to 1.6±0.2*10–7K1(min–1) and from 1.04±0.2*10–5 K2(M –1 min–1) to 1.5± 0.3*10–4 K2(M –1min–1), respectively for autocatalytic model. Limitation step of the reaction is the nucleation. K1
اطلاعات انتشار: Journal of Applied Biotechnology Reports، دوم،شماره۲، Spring ۲۰۱۵، سال ۰
تعداد صفحات: ۶
The aggregation of protein is the most prevalent and the most disturbing kind of instability and this challenge exists in almost every stage of the development of protein drug. The presence of insoluble aggregations in protein drugs will make the supply of the product a tough job. This study identifies the inhibition of the folded Interferon beta 1–b’s aggregation with the assistance of some excipients. It uses some thermal stress and mechanical methods to accelerate the aggregation, and also the spectroscopic method to identify the protein aggregation and its growth. Experimental data of the tests show compliance with the autocatalytic model. This model has been used to obtain the Kinetic constants of aggregation in different states and to make comparison with one another in the presence of some excipients. The kinetic constants were obtained by fitting the Autocatalytic model on data. Among these excipients, Polysorbate 20 of 0.01% (w\v) showed the best result in decreasing the aggregation. Using this excipient of 0.01% (w\v) in thermal stress causes dramatic reduction of nucleation constant from 8.3× 10–3 (min–1) to 4.14× 10–6 (min–1), which indicates the reduction of protein aggregation in the solution.
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