Optimization of the Methods to Develop Stable Polymer Gels for Water Management in Medium- and Ultra-High-Salinity Reservoirs.
作者: Shuiqing Hu ; Mingchen Ding ; Yafei Hu ; Yefei Wang ; Jiangyang Dong
Polymer gels suffer from a serious syneresis issue when exposed to high-temperature and high-salinity (HTHS) conditions, which limits their use as water-treatment agents in this type of reservoir. In this paper, the effects of the polymer type/concentration, deoxidizers, and stabilizers on the long-term stability of polymer gels were systematically studied; thus, the methods to develop stable polymer gels for two typical levels of salinity were optimized. The results show the following: (1) For a medium-salinity condition (TDS: 33,645.0 mg/L) at 125 °C, conventional HPAM gels completely dehydrate within only 1 day, and the addition of a deoxidizer hardly improved their stability. Some special polymers, e.g., AP-P5, MKY, and CPAM, are able to form stable gels if a high concentration of 0.8% is used; the syneresis rate of these gels is about 10% after 30 days. However, the addition of the complexant sodium oxalate significantly improves the stability of gels formed by all five of these different polymers, which behave with a 0% syneresis rate after 30 days pass. Complexants are the most economical and feasible agents to develop stable gels in medium-salinity water. (2) Gels enhanced using the methods above all become unstable in a more challenging ultra-high-saline condition (TDS: 225,068.0 mg/L). In this case, special calcium- and magnesium-resistant polymers are required to prepare stable gels, which show 0% syneresis rates after 30 days, have relatively low strengths, but do produce a good plugging effect in high-permeability cores.
Response surface optimization of chemical coagulation for solid-liquid separation of dairy manure slurry through Box-Behnken design with desirability function
Discharging livestock manure slurry without proper treatment causes various environmental and sociological problems. Chemical coagulation is a widely used and easily applicable method for treating such wastewater. However, the technique requires optimization to enhance coagulation efficiency while minimizing chemical usage. In this study, we propose an efficient, low-cost, and environmentally safe chemical coagulation method for solid-liquid separation of dairy manure slurry. Experiments were conducted in laboratory jar tests using dairy manure slurry to investigate the impact of coagulants, specifically polyaluminum chloride (PAC) and cationic polyacrylamide (CPAM), as well as pH, on the process of solid-liquid separation. Preliminary ranges of PAC, CPAM, and pH were estimated through single-factor experiments. Coagulation optimization and modeling were performed using the response surface methodology (RSM) with the Box-Behnken design (BBD), wherein the desired goal of each parameter was set to maximize solid-liquid separation efficiency while reducing chemical dosage to maintain residual aluminum (Al) concentrations below water quality standards. Numerical optimization predicted that the optimal dosages were 75 mg/L of PAC and 35 mg/L of CPAM at pH 7. Under these conditions, removal efficiencies of 99% for turbidity and 97% for chemical oxygen demand (COD) were achieved, with a minimal residual Al concentration of 0.045 mg/L. Positive zeta potential values in the treated water confirmed complete separation of negatively charged solids in the dairy manure slurry. The response values predicted by BBD aligned with the experimental results, and the analysis of variance (ANOVA) demonstrated the predictability and accuracy of the response models. Consequently, this study highlights the practical application of RSM with BBD in optimizing chemical coagulation using PAC and CPAM to achieve efficient solid-liquid separation in livestock wastewater while maintaining low residual Al concentrations.
Optimization Conditions to Obtain Cationic Polyacrylamide Emulsion Copolymers with Desired Cationic Degree for Different Wastewater Treatments.
作者: Tung Huy Nguyen ; Linh Pham Duy Nguyen ; Thao Thi Phuong Nguyen ; Minh Xuan Anh Le ; Linh Thi Thuy Kieu ; Huong Thi To ; Thanh Tien Bui
The synthesis of cationic polyacrylamides (CPAMs) with the desired cationic degree and molecular weight is essential for various industries, including wastewater treatment, mining, paper, cosmetic chemistry, and others. Previous studies have already demonstrated methods to optimize synthesis conditions to obtain high-molecular-weight CPAM emulsions and the effects of cationic degrees on flocculation processes. However, the optimization of input parameters to obtain CPAMs with the desired cationic degrees has not been discussed. Traditional optimization methods are time-consuming and costly when it comes to on-site CPAM production because the input parameters of CPAM synthesis are optimized using single-factor experiments. In this study, we utilized the response surface methodology to optimize the synthesis conditions, specifically the monomer concentration, the content of the cationic monomer, and the content of the initiator, to obtain CPAMs with the desired cationic degrees. This approach overcomes the drawbacks of traditional optimization methods. We successfully synthesized three CPAM emulsions with a wide range of cationic degrees: low (21.85%), medium (40.25%), and high (71.17%) levels of cationic degree. The optimized conditions for these CPAMs were as follows: monomer concentration of 25%, content of monomer cation of 22.5%, 44.41%, and 77.61%, respectively, and initiator content of 0.475%, 0.48%, and 0.59%, respectively. The developed models can be utilized to quickly optimize conditions for synthesizing CPAM emulsions with different cationic degrees to meet the demands of wastewater treatment applications. The synthesized CPAM products performed effectively in wastewater treatment, with the treated wastewater meeting the technical regulation parameters. 1H-NMR, FTIR, SEM, BET, dynamic light scattering, and gel permeation chromatography were employed to confirm the structure and surface of the polymers.
ALG-055009, a THR-β agonist drug candidate in development as a treatment for NASH, demonstrated dose-dependent reductions in several atherogenic lipids and a favorable pharmacokinetic profile in subjects with hyperlipidemia Aligos’ oral and poster presentations also collectively highlight new data from the company’s drug candidates targeting PD-L1 inhibition and the CAM-A (CAM-aberrant) mechanism for the treatment of chronic hepatitis B (CHB) SOUTH SAN FRANCISCO, Calif., Nov. 04, 2022 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, today announced that the company is presenting several posters and an oral presentation at The Liver Meeting® (November 4-8, 2022), hosted by the American Association for the Study of Liver Diseases (AASLD). Notably, poster 2354 provides new data on the activity of ALG-055009, Aligos’ thyroid hormone receptor beta (THR-β) agonist in development for nonalcoholic steatohepatitis (NASH). Multiple ascending dose (MAD) data from the ongoing Phase 1 study ALG-055009-301 (NCT05090111) demonstrate that treatment for 14 days in subjects with hyperlipidemia resulted in reduced triglyceride, low-density lipoprotein (LDL), and apolipoprotein B levels in a generally dose-dependent manner. ALG-055009 was well tolerated and resulted in favorable dose-proportional pharmacokinetics with low inter-subject variability across the therapeutic range. “We are pleased with the emerging clinical profile of ALG-055009,” said Lawrence Blatt, Ph.D., MBA, CEO and Chairman of the Board at Aligos. “THR-β agonists continue to have the potential to become a cornerstone therapy in the treatment of NASH and ALG-055009 appears to benchmark favorably with other drugs in this class. Moving forward, we plan to evaluate its ability to reduce fat in the livers of subjects with NASH over a twelve-week period in a Phase 2 study funded internally or through a partnership.” Aligos’ oral and poster presentations at The Liver Meeting collectively highlight new data from the company’s drug candidates targeting chronic hepatitis B (CHB) and nonalcoholic steatohepatitis (NASH) and are available on the Aligos website at Scientific Presentations & Conferences. Presentation details are described below. Aligos has highlighted new Phase 1 clinical data on its CAM-E drug candidate, ALG-000184, in a separate press release. Presentation Details NASH THR-β agonist Title: Safety, Pharmacokinetics, and Pharmacodynamics of multiple ascending oral doses of ALG-055009, a thyroid hormone receptor beta agonist, in hyperlipidaemic subjects Publication Number: 2354Presenter: Hakim Charfi, M.D. Summary: See above. Chronic Hepatitis B PD-L1 inhibitor: small molecule Title: Discovery of liver-targeted oral PDL1 small molecule inhibitors for the treatment of chronic hepatitis B and liver cancers Presentation Number: 34890Publication Number: 26Presenter: Tongfei Wu, Ph.D.Summary: The authors rationally designed liver-targeted oral PD-L1 small molecule inhibitors to localize T cell activation in the liver and thereby potentially mitigate systemic toxicity, toward an effort to develop better tolerated PD1/PD-L1 inhibitors for CHB patients. Lead molecules developed to date show similar in vivo efficacy to approved antibodies, but were more efficacious than antibodies in a liver metastatic tumor model. PD-L1 inhibitor: siRNA Title: Suppression of PD-L1 expression by a novel liver-targeted siRNA leads to potential restoration of immune responses against HBV Poster Number: 36189Publication number: 1186Presenter: Jin Hong, Ph.D.Summary: Liver-targeted PD-L1 siRNA therapy may lead to restoration of immune responses against HBV and consequent clearance of HBV infection, which is considered critical for CHB cure. Multiple siRNAs with sub-nanomolar PD-L1 mRNA inhibition EC50 values have been identified. Efforts to identify siRNAs with greater PD-L1 expression knockdown efficiency as well as greater anti-HBV activity are ongoing. CAM-A Title: Non-HAP class I capsid assembly modulators have distinct profiles and a differentiated mechanism of action Poster Number: 37007Publication number: 1208Presenter: Yannick Debing, Ph.D.Summary: Non-HAP (heteroaryldihydropyrimidine) CAM-1 (CAM-A, or CAM-aberrant) compounds ALG-005398 and ALG-006162 have a profile that is clearly distinct from known HAP CAM-1s. Data presented here suggest that non-HAP CAM-1s can promote HBsAg reduction via a mechanism distinct from that of HAP CAM-1s. As optimized non-HAP CAM-1s have suitable ADME/toxicity profiles, they represent an attractive class of molecules for further development as a part of potential functional cure regimens for CHB. Title: HAP Class I capsid assembly modulators clear hepatitis B virus-infected hepatocytes through core-dependent hepatocyte death and subsequent proliferation Poster Number: 36810Publication Number: 1202Presenter: Dieudoneé Buh Kum, Ph.D.Summary: In vivo and in vitro HAP CAM-1 (CAM-A, or CAM-aberrant) RG7907 was shown to act through two mechanisms, possibly complemented by an immune response, that result in a sustained loss of HBV-positive cells. First, RG7907 was shown to induce hepatitis B virus (HBV) core protein (HBc) aggregation and hepatocyte apoptosis in HBc-expressing cells. Second, compensatory hepatocyte proliferation was shown to lead to an additional loss of AAV-HBV episomes. This represents an attractive mechanism for regimens intended to introduce functional cure in CHB. siRNA Title: Nonclinical efficacy, pharmacokinetic profile and pharmacokinetic/pharmacodynamic (PK/PD) correlation of ALG-125755, a GaINAc-conjugated siRNA, for functional cure of chronic hepatitis B Poster Number: 35097Publication Number: 1155Presenter: Kusum Gupta Summary: ALG-125755 demonstrates encouraging preclinical pharmacology, PK/PD properties, and a long half-life in the liver, which predicts monthly or less frequent dosing in human subjects. A Phase 1 study of ALG-125755 began dosing in healthy volunteers in Oct 2022. About Aligos Aligos Therapeutics, Inc. is a clinical stage biopharmaceutical company that was founded in 2018 with the mission to become a world leader in the treatment of viral infections and liver diseases. Aligos is focused on the discovery and development of targeted antiviral therapies for chronic hepatitis B (CHB) and coronaviruses as well as leveraging its expertise in liver diseases to create targeted therapeutics for nonalcoholic steatohepatitis (NASH). Aligos’ strategy is to harness the deep expertise and decades of drug development experience its team has in liver disease, particularly viral hepatitis, to rapidly advance its pipeline of potentially best-in-class molecules. Forward-Looking Statement This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered “forward-looking statements,” including without limitation, statements regarding THR-β agonists continuing to have the potential to become a cornerstone therapy in the treatment of NASH; ALG-055009 appearing to benchmark favorably with other drugs in this class and our plan to evaluate its ability to reduce fat in the livers of subjects with NASH over a twelve-week period in a Phase 2 study funded internally or through a partnership. Forward-looking statements are typically, but not always, identified by the use of words such as “may,” “will,” “would,” “believe,” “intend,” “plan,” “anticipate,” “estimate,” “expect,” and other similar terminology indicating future results. Such forward looking statements are subject to substantial risks and uncertainties that could cause our development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including Aligos’ clinical-stage of development, the process of designing and conducting clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Aligos’ ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of Aligos’ capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape and the effects on our business of the worldwide COVID-19 pandemic and the ongoing conflict between Russia and Ukraine. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Aligos in general, see Aligos’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 2, 2022 and its future periodic reports to be filed or submitted with the Securities and Exchange Commission. Except as required by law, Aligos undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events. Media ContactAmy Jobe, Ph.D.LifeSci Communications+1 315 879 email@example.com Investor ContactCorey Davis, Ph.D.LifeSci Advisors+1 212 915 firstname.lastname@example.org
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In its third-quarter report Tuesday, Roche announced it has cut two Phase II programs, one for hepatitis B and the other for geographic atrophy, a form of eye disease.
RG7907 is a core protein allosteric modulator that was developed for hepatitis B. Early data suggested the drug disrupted hepatitis B viral replication, and a Phase I trial in 2019 led the company to believe it could be part of a combination of drugs that could cure the disease.
A Phase I trial was completed in July, and a Phase II trial of the drug in combination with other therapies was ongoing as of August.
Roche Diagnostics has several assays to detect hepatitis B and several pipeline drugs, including RG6084, RG6346 and RG7854.
RG6147 (galegenimab), an anti-HTRA1 anti-binding fragment, was being developed for geographic atrophy.
The Phase II trial launched in June 2019 and as of September, its status was “active, not recruiting.”
Roche also has a very active program for ophthalmological conditions, including macular degeneration and geographic atrophy.
In a statement, CEO Severin Schwan specifically cited Vabysmo. The drug is the first and only FDA-approved treatment that blocks both VEGF and Ang-2 in wet age-related macular degeneration and diabetic macular edema. It was approved in Europe in the third quarter of this year.
Roche's subsidiary Chugai Pharmaceutical removed a Phase II program of a CHU Oncolytic Type 5 adenovirus for esophageal cancer. These types of viruses are designed to selectively grow in tumor cells, killing them while minimizing disruptions to normal cells.
Other Business Updates
Roche reported 2% sales growth, despite what Schwan in a press conference called “the expected sharp decline in COVID-19-related products in both divisions in the third quarter.
"The demand for our newer medicines for multiple sclerosis, hemophilia, spinal muscular atrophy and cancer remains high," he said.
COVID-19 drug sales dropped by $1 billion (U.S.) in the first nine months of the year. Those included Ronapreve, an antibody treatment, and Actemra, originally developed for arthritis.
Roche Diagnostics also reported a 40% decrease in COVID-19-related tests year on year to $604,000.
“In spite of increasing incidence rates for COVID-19, we actually don’t see an increase in the demand for COVID-19-related products. It has nothing to do with inventories … there is simply much smaller demand than we have seen in the previous year," Schwan said.
Clinical trial data for Roche's Alzheimer’s drug gantenerumab is expected to be published by the end of November, the company noted.
Since the announcement of positive Phase III data from Eisai and Biogen’s lecanemab for Alzheimer’s disease in late September, analysts and investors have been turning their focus to gantenerumab in a suddenly hopeful market.
If anything, Schwan worked to keep expectations low, saying, “It is very dangerous to cross-read on trials. We have to wait for the readout, and then we can take it from there.”
Jefferies analysts were pessimistic, writing in a note to investors that they expect the study to fail.