Glucagon for Injection is a polypeptide hormone medication used to treat patients with severe hypoglycemia or low blood sugar. Only recently, was a generic version of glucagon for injection approved ...by the FDA. While the generic version was deemed equivalent to its brand-name counterpart, the two glucagon products were produced using different manufacturing processes. The brand-name glucagon is produced via recombinant DNA while the generic glucagon is produced by peptide synthesis. Different manufacturing processes can result in different levels of innate immune response modulating impurities (IIRMIs). This study utilized a cell-based assay method, which allows for detection of a broad spectrum of impurities, to investigate the IIRMI risks of the generic glucagon to make sure it has similar or less immunogenicity risks than the brand-name glucagon product. Three commercial cell lines (RAW-Blue™, HEK-Blue™-hNOD1 and HEK-Blue™-hNOD2) carrying a secreted embryonic alkaline phosphatase reporter construct were used to quantify the level of innate immune responses after being treated with the glucagon drugs. The study results showed that despite differences in manufacturing process, the innate immunogenicity risk in the synthetic (generic) glucagon was at negligible level and comparable to the recombinant (brand-name) glucagon product.
Recently, the first generic glucagon for injection was approved for the treatment of severe hypoglycemia. Unlike its brand name recombinant glucagon, the generic glucagon is synthetic. Since glucagon ...has a high propensity to form aggregates in solution, it is essential to assess the aggregation profile of the synthetic glucagon compared to the recombinant glucagon. In this study, two robust separation methods, size-exclusion chromatography (SEC-HPLC) and field-flow fractionation coupled with a multi-angle light scattering detector (FFF-MALS), were employed to characterize generic and brand glucagon aggregation in six lots (three newly released, three expired). The presence of aggregation in samples was determined from the generated chromatograms and analyzed. The study showed that both products have comparable aggregation profiles. The SEC-HPLC demonstrated that in both glucagon versions, the expired lots had a higher percentage of dimers than the newly released lots, but even at expiration, the amount was negligible (∼0.1%). The FFF-MALS method did not detect any dimers or higher molecular weight aggregates. Further evaluation of the detection limit found that FFF-MALS was unable to detect aggregates at amounts lower than 0.5% of total glucagon. The negligible amounts of dimer detected in the generic and brand glucagon indicate that both versions are physically stable and are not prone to aggregation under clinically relevant conditions.
Glucagon for Injection is a polypeptide hormone medication used to treat patients with severe hypoglycemia or low blood sugar. Only recently, was a generic version of glucagon for injection approved ...by the FDA. While the generic version was deemed equivalent to its brand-name counterpart, the two glucagon products were produced using different manufacturing processes. The brand-name glucagon is produced via recombinant DNA while the generic glucagon is produced by peptide synthesis. Different manufacturing processes can result in different levels of innate immune response modulating impurities (IIRMIs). This study utilized a cell-based assay method, which allows for detection of a broad spectrum of impurities, to investigate the IIRMI risks of the generic glucagon to make sure it has similar or less immunogenicity risks than the brand-name glucagon product. Three commercial cell lines (RAW-Blue™, HEK-Blue™-hNOD1 and HEK-Blue™-hNOD2) carrying a secreted embryonic alkaline phosphatase reporter construct were used to quantify the level of innate immune responses after being treated with the glucagon drugs. The study results showed that despite differences in manufacturing process, the innate immunogenicity risk in the synthetic (generic) glucagon was at negligible level and comparable to the recombinant (brand-name) glucagon product.
Glucagon, a 29-amino acid polypeptide hormone, is an essential therapeutic agent used in the emergency treatment of hypoglycemia. However, glucagon is inherently unstable in aqueous solution. While ...glucagon equilibrates between unordered and the secondary α-helix state in solution, it can quickly transform into a different secondary β-sheet-rich amyloid-like fibril/oligomer structure under various conditions. Since changes in the secondary structure of glucagon can cause significant impacts, structure analysis is necessary and essential to assess the safety of the product. This study analyzed the secondary structure of glucagon products at the release and at the expiry using circular dichroism spectroscopy (CD) and 2D Nuclear Overhauser effect spectroscopy (2D NOESY). In order to also determine if structural differences exist between glucagon produced through different manufacturing processes, synthetic and recombinant glucagon products were used and compared. The CD results indicated that for all release and expired glucagon products, the structure compositions were 14 to 16% α-helix, 17 to 19% β-strand, 14 to 15% Turn, and 53 to 54% Unordered. This was consistent with the 2D NOESY analysis which showed that both products had an approximate α-helix composition of 14 to 17%. Overall, there were no significant differences in terms of the secondary structure between synthetic and recombinant glucagon products both at the release and at the expiry.
Glucagon is a polypeptide hormone that serves as an essential therapeutic agent in the emergency treatment of hypoglycemia. Recently, the first generic glucagon for injection was approved. However, ...unlike its brand name counterpart, which is produced via recombinant DNA, the generic glucagon is produced using a chemical synthesis method. Regardless of its origin, impurities may occur in both glucagon drug products. While these impurities may greatly compromise the safety and efficacy of the glucagon drug products, studies accessing the impurities of glucagon for injection are limited. This manuscript analyzed the stability and impurities of a generic and brand glucagon for injection, including desamido and non-desamido impurities, under various storage and temperature conditions using an ultra-performance liquid chromatography method. The glucagon products were analyzed after 6 and 24 months of storage under room temperatures (20–25 °C). In addition, the products were also assessed after 6 months of storage under high temperatures (40 °C). Under each stability storage condition, three lots of the synthetic glucagon were evaluated by UPLC with at least one lot of the recombinant glucagon for comparison. A total of 37 peaks were identified (except for the solvent peaks, which appeared at retention times less than 1.5 min) from the synthetic and recombinant glucagon lots. It was found that the number of impurities observed in the synthetic glucagon were lower than the referenced recombinant glucagon across all stability conditions. Throughout all tested conditions, the synthetic glucagon for injection had an averaged purity of 92.8–99.3%, while the referenced recombinant drug had an averaged purity of 70.3–91.7%. Based on the study results, it can be concluded that the impurity profile for the synthetic glucagon for injection has a comparable and even lower level of impurities than the recombinant version under all stability conditions.
In this study, synthesis of water soluble and efficient corrosion inhibitors PBTB carrying single benzotriazole part and PDBTB containing double benzotriazole segments for copper in 3.5 wt% sodium ...chloride solution was proposed. PDBTB showed greater corrosion inhibition effect than PBTB basing on survey results of polarization curves, impedance spectroscopy and scanning electron microscopy. Adsorption mechanism of the studied inhibitors on copper surface was studied by FT-IR spectra, X-ray photoelectron spectroscopy, X-ray diffraction spectra as well as adsorption isotherm.
The recovery of butyl acetate (BA) from lovastatin wastewater was studied by using the method of solvent extraction with liquid paraffin (LP) as the extractant. The effect of several key factors on ...the extraction efficiency including lysozyme content, initial BA concentration, equilibration time, and phase ratio was investigated. The results showed that the extraction efficiency of BA can reach 98% in 15
min at room temperature when the initial concentration of BA is 7000
mg/L. The loading capability of LP was demonstrated to be high by reusing the loaded LP to extract the fresh wastewater. Moreover, BA in the LP phase can be effectively recovered by vacuum evaporation and the regenerated LP has a very good reusability.
► The results of extraction of butyl acetate with liquid paraffin are satisfactory. ► Butyl acetate in the loaded liquid paraffin can be recovered by vacuum evaporation. ► The used LP can be regenerated by alkali treatment and it has a good reusability.
Pair trading is one of the main methods of statistical arbitrage, mainly by taking advantage of the temporary price anomalies between related financial products with long-term equilibrium ...relationships to obtain arbitrage opportunities. In this paper, based on the co-integration method for the selection of allotment, the deep reinforcement learning method is integrated. The deep reinforcement learning method establishes an autonomous learning model and develops paired trading rules under different cycles. At the same time, the deep neural network model is used to implement the learning and training algorithm. This paper uses the data of Shanghai Commodity Exchange and Dalian Commodity Exchange on black futures, and the period is from January 2, 2014 to December 31, 2021. Three different periods were set for five models, namely simple threshold method (ST), simple threshold method based on pairwise cointegration (CA-ST), simple threshold method based on tripartite Cointegration (CA-ST-ALL), deep reinforcement learning method (DRL), and Deep reinforcement learning method based on pairwise cointegration (CA-DRL), and economic indicators were compared. The final results show that, combining the results of the three time periods, the deep reinforcement learning method based on pairwise cointegration performs better regarding return and risk control, validating the feasibility of deep reinforcement learning in China's future market.
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•Novel amphiphilic topological hyperbranched polymers were synthesized.•Self-assembly of the target polymers were obtained in aqueous sulfuric acid solution.•Chemical adsorption of ...the target macromolecular assemblies on copper was investigated.•Neat corrosion resistance of the target macromolecular assemblies for copper in acid medium was affirmed.
Novel topological hyperbranched polymers (THPs) with large polymer molecular weight and narrow polydispersities are synthesized in this study by using 1,3,5-tri(methyl bromide)-benzene and phenylmethyl-linked bisimidazole or triimidazole as the starting monomers. The results show that the THPs can process regular molecular assembly in mixed ethanol/sulfuric acid aqueous solution. The sizes and morphologies of the THPs aggregates are shown dependence on the assembly concentrations and aggregation evolution time. The Cu(I)-N chemical bonding formed by the THPs assemblies and copper ions is demonstrated by the comprehensive surface analysis, and the bonding makes the primary contribution to produce chemisorption layer on copper substrate. The electrochemical measurements reveal the super copper corrosion inhibition capability of the robust THPs assemblies protective layers in sulfuric acid solution. In addition, the effects of corrosion temperature on corrosion resistance, the kinetic parameters and the Langmuir isotherms indicate the possible presence of physisorption. The adsorption process of THPs aggregates on copper surface is further understood by the molecular modeling and the molecular dynamics simulation. The gained results in this study could provide a new thought of designing and synthesizing benign and effective polymer materials for anti-corrosion copper in harsh aggressive acid media.
With crucial roles on the differentiation of anterior pituitary and the regulation of the prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone-beta (TSH-beta) genes, the chicken PIT1 ...gene is regarded as a key candidate gene for production traits. In this study, five reported polymorphisms (MR1-MR5) of the PIT1 gene were genotyped in a full sib F2 resource population to evaluate their effects on growth, carcass and fatty traits in chickens.
Marker-trait association analyses showed that, MR1 was significantly associated with shank diameters (SD) at 84 days (P < 0.05), hatch weight (HW) and shank length (SL) at 84 days (P < 0.01), MR2 was significantly associated with BW at 28, 42 days and average daily gain (ADG) at 0-4 weeks (P < 0.05), and MR3 was significantly associated with ADG at 4-8 weeks (P < 0.05). MR4 was associated with SL at 63, 77, 84 days and BW at 84 days (P < 0.05), as well as SD at 77 days (P < 0.01). Significant association was also found of MR5 with BW at 21, 35 days and SD at 63 days (P < 0.05), BW at 28 days and ADG at 0-4 weeks (P < 0.01). Both T allele of MR4 and C allele of MR5 were advantageous for chicken growth. The PIT1 haplotypes were significantly associated with HW (P = 0.0252), BW at 28 days (P = 0.0390) and SD at 56 days (P = 0.0400). No significant association of single SNP and haplotypes with chicken carcass and fatty traits was found (P > 0.05).
Our study found that polymorphisms of PIT1 gene and their haplotypes were associated with chicken growth traits and not with carcass and fatty traits.
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