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Alimentary Pharmacology & Therapeutics Jun 2000Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic... (Review)
Review
Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate-based raft-forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate-based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH-neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro-oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate-based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents. The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate-containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate-based raft-forming formulations can additionally provide longer-lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms. Alginate-based, raft-forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate-rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non-systemic mechanism of action provides rapid and long-duration relief of heartburn and acid reflux symptoms.
Topics: Adult; Alginates; Aluminum Hydroxide; Antacids; Carbon Dioxide; Child; Cost-Benefit Analysis; Drug Combinations; Female; Gastric Acid; Gastroesophageal Reflux; Heartburn; Humans; Infant; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Proton Pumps; Silicic Acid; Sodium Bicarbonate
PubMed: 10848650
DOI: 10.1046/j.1365-2036.2000.00759.x -
Molecules (Basel, Switzerland) Jul 2023In this study, LiNiCoAlO@x%AlOcoated cathode materials were regeneratively compounded by the solid-phase sintering method, and their structural characterization and...
In this study, LiNiCoAlO@x%AlOcoated cathode materials were regeneratively compounded by the solid-phase sintering method, and their structural characterization and electrochemical performance were systematically analyzed. The regenerated ternary cathode material precursor synthesized by the co-precipitation method was roasted with lithium carbonate at a molar ratio of 1:1.1, and then completely mixed with different contents of aluminum hydroxide. The combined materials were then sintered at 800 °C for 15 h to obtain the regenerated coated cathode material, LiNiCoAlO@x%AlO. The thermogravimetry analysis, phase composition, morphological characteristics, and other tests show that when the added content of aluminum hydroxide is 3%, the regenerated cathode material, [email protected]%AlO exhibits the highest-order layered structure with AlO coating. This material can better inhibit the production of Ni, and improve material structure and electrochemical properties. The first charge-discharge efficiency of the battery assembled with this regenerated cathode material is 97.4%, a 50-cycle capacity retention is 93.4%, and a 100-cycle capacity retention is 87.6%. The first charge-discharge efficiency is far better than that of the uncoated regenerated battery.
Topics: Lithium; Aluminum Hydroxide; Lithium Carbonate; Body Fluids; Electrodes; Ions
PubMed: 37446830
DOI: 10.3390/molecules28135165 -
European Journal of Pharmaceutics and... Mar 2019No United States Food and Drug Administration-licensed vaccines protective against Ebola virus (EBOV) infections are currently available. EBOV vaccine candidates...
No United States Food and Drug Administration-licensed vaccines protective against Ebola virus (EBOV) infections are currently available. EBOV vaccine candidates currently in development, as well as most currently licensed vaccines in general, require transport and storage under a continuous cold chain in order to prevent potential decreases in product efficacy. Cold chain requirements are particularly difficult to maintain in developing countries. To improve thermostability and reduce costly cold chain requirements, a subunit protein vaccine against EBOV was formulated as a glassy solid using lyophilization. Formulations of the key antigen, Ebola glycoprotein (EBOV-GP), adjuvanted with microparticulate aluminum hydroxide were prepared in liquid and lyophilized forms, and the vaccines were incubated at 40 °C for 12 weeks. Aggregation and degradation of EBOV-GP were observed in liquid formulations during the 12-week incubation period, whereas changes were minimal in lyophilized formulations. Antibody responses against EBOV-GP following three intramuscular immunizations in BALB/c mice were used to determine vaccine immunogenicity. EBOV-GP formulations were equally immunogenic in liquid and lyophilized forms. After lyophilization and reconstitution, adjuvanted vaccine formulations produced anti-EBOV-GP IgG antibody responses in mice similar to those generated against corresponding adjuvanted liquid vaccine formulations. More importantly, antibody responses in mice injected with reconstituted lyophilized vaccine formulations that had been incubated at 40 °C for 12 weeks prior to injection indicated that vaccine immunogenicity was fully retained after high-temperature storage, showing promise for future vaccine development efforts.
Topics: Aluminum Hydroxide; Animals; Drug Compounding; Drug Stability; Ebola Vaccines; Ebolavirus; Female; Freeze Drying; Hemorrhagic Fever, Ebola; Mice; Mice, Inbred BALB C
PubMed: 30703544
DOI: 10.1016/j.ejpb.2019.01.019 -
Frontiers in Cellular and Infection... 2022Leptospirosis is a neglected disease of man and animals that affects nearly half a million people annually and causes considerable economic losses. Current human...
Leptospirosis is a neglected disease of man and animals that affects nearly half a million people annually and causes considerable economic losses. Current human vaccines are inactivated whole-cell preparations (bacterins) of spp. that provide strong homologous protection yet fail to induce a cross-protective immune response. Yearly boosters are required, and serious side-effects are frequently reported so the vaccine is licensed for use in humans in only a handful of countries. Novel universal vaccines require identification of conserved surface-exposed epitopes of leptospiral antigens. Outer membrane β-barrel proteins (βb-OMPs) meet these requirements and have been successfully used as vaccines for other diseases. We report the evaluation of 22 constructs containing protein fragments from 33 leptospiral βb-OMPs, previously identified by reverse and structural vaccinology and cell-surface immunoprecipitation. Three-dimensional structures for each leptospiral βb-OMP were predicted by I-TASSER. The surface-exposed epitopes were predicted using NetMHCII 2.2 and BepiPred 2.0. Recombinant constructs containing regions from one or more βb-OMPs were cloned and expressed in . IMAC-purified recombinant proteins were adsorbed to an aluminium hydroxide adjuvant to produce the vaccine formulations. Hamsters (4-6 weeks old) were vaccinated with 2 doses containing 50 - 125 μg of recombinant protein, with a 14-day interval between doses. Immunoprotection was evaluated in the hamster model of leptospirosis against a homologous challenge (10 - 20× ED) with serogroup Icterohaemorrhagiae serovar Copenhageni strain Fiocruz L1-130. Of the vaccine formulations, 20/22 were immunogenic and induced significant humoral immune responses (IgG) prior to challenge. Four constructs induced significant protection (100%, < 0.001) and sterilizing immunity in two independent experiments, however, this was not reproducible in subsequent evaluations (0 - 33.3% protection, > 0.05). The lack of reproducibility seen in these challenge experiments and in other reports in the literature, together with the lack of immune correlates and commercially available reagents to characterize the immune response, suggest that the hamster may not be the ideal model for evaluation of leptospirosis vaccines and highlight the need for evaluation of alternative models, such as the mouse.
Topics: Cricetinae; Humans; Mice; Animals; Aluminum Hydroxide; Reproducibility of Results; Leptospirosis; Leptospira; Bacterial Vaccines; Antigens, Bacterial; Recombinant Proteins; Escherichia coli; Immunoglobulin G; Epitopes
PubMed: 36275031
DOI: 10.3389/fcimb.2022.940966 -
The Journal of Clinical Investigation Apr 2024BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).
Topics: Adult; Humans; Malaria Vaccines; Plasmodium falciparum; Protozoan Proteins; Adjuvants, Immunologic; Antigens, Protozoan; Aluminum Hydroxide; Antibodies, Protozoan; Malaria; Malaria, Falciparum
PubMed: 38290009
DOI: 10.1172/JCI175707 -
Vaccine Jan 2017There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3... (Comparative Study)
Comparative Study Randomized Controlled Trial
First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.
BACKGROUND
There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans.
METHODS
240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority.
IMMUNOGENICITY RESULTS
The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial.
SAFETY RESULTS
No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447.
Topics: Adjuvants, Immunologic; Adolescent; Aluminum Hydroxide; Antibodies, Viral; Child; Child, Preschool; Denmark; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunization, Secondary; Infant; Male; Poliomyelitis; Poliovirus Vaccine, Inactivated
PubMed: 28027810
DOI: 10.1016/j.vaccine.2016.12.027 -
Journal of Nanobiotechnology Oct 2023Current protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development...
Current protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development of implantable memristor devices. It is imperative to discover novel candidate materials for biomemristor with high durability and excellent biosafety for implantable health monitoring. Herein, we initially demonstrate the resistance switching characteristics of a nonvolatile memristor in a configuration of Pt/AlOOH/ITO consisting of biocompatible AlOOH nanosheets sandwiched between a Indium Tin Oxides (ITO) electrode and a platinum (Pt) counter-electrode. The hydrothermally synthesized AlOOH nanosheets have excellent biocompatibility as confirmed through the Cell Counting Kit-8 (CCK-8) tests. Four discrete resistance levels are achieved in this assembled device in responsible to different compliance currents (I) for the set process, where the emerging multilevel states show high durability over 10 cycles, outperforming the protein-based biomemristors under similar conditions. The excellent performance of the Pt/AlOOH/ITO memristor is attributed to the significant role of hydrogen proton with pipe effect, as confirmed by both experimental results and density functional theory (DFT) analyses. The present results indicate the nonvolatile memristors with great potential as the next generation implantable multilevel resistive memories for long-term human health monitoring.
Topics: Humans; Aluminum Hydroxide; Aluminum Oxide; Biological Products
PubMed: 37833677
DOI: 10.1186/s12951-023-02117-5 -
Molecules (Basel, Switzerland) Oct 2022An unprecedented route for mitigating the inhibitory effect of lactic acid (LA) on milk fermentation was achieved through lactate adsorption on hydrotalcite (Ht) from...
An unprecedented route for mitigating the inhibitory effect of lactic acid (LA) on milk fermentation was achieved through lactate adsorption on hydrotalcite (Ht) from simulated lactate extracts. During its regeneration by ozonation, Ht displayed catalytic activity that appeared to increase by addition of montmorillonite (Mt). Changes in the pH, Zeta potential and catalyst particle size during LA ozonation were found to strongly influence LA-LA, LA-catalyst and catalyst-catalyst interactions. The latter determine lactate protonation-deprotonation and clay dispersion in aqueous media. The activity of Mt appears to involve hydrophobic adsorption of non-dissociated LA molecules on silica-rich areas at low pH, and Lewis acid-base and electrostatic interactions at higher pH than the pKa. Hydrotalcite promotes both hydrophobic interaction and anion exchange. Hydrotalcite-smectite mixture was found to enhance clay dispersion and catalytic activity. This research allowed demonstrating that natural clay minerals can act both as adsorbents for LA extract from fermentation broths and as catalysts for adsorbent regeneration. The results obtained herein provide valuable and useful findings for envisaging seed-free milk clotting in dairy technologies.
Topics: Adsorption; Aluminum Hydroxide; Animals; Bentonite; Catalysis; Clay; Fermentation; Lactic Acid; Lewis Acids; Magnesium Hydroxide; Milk; Minerals; Ozone
PubMed: 36235039
DOI: 10.3390/molecules27196502 -
Vaccine Nov 2021COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases...
COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4 T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).
Topics: Alum Compounds; Aluminum Hydroxide; Animals; Antibodies, Neutralizing; Antibodies, Viral; CHO Cells; COVID-19; COVID-19 Vaccines; Cricetinae; Cricetulus; Humans; Mice; Pandemics; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 34750014
DOI: 10.1016/j.vaccine.2021.10.066 -
Clinical and Vaccine Immunology : CVI Nov 2013Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for...
Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as the free phosphate concentration increased, and the binding of rPA changed from endothermic to exothermic. Crucially, phosphate restored the thermostability of bound rPA so that it resembled the soluble form, even though it remained tightly bound to the surface. Batches of vaccine with either 0.25 mM (subsaturated) or 4 mM (saturated) phosphate were tested in a disease model at batch release, which showed that the latter was significantly more potent. Both formulations retained their potency for 3 years. The strongest aluminum adjuvant effects are thus likely to be via weakly attached or easily released native-state antigen proteins.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Anthrax; Anthrax Vaccines; Antigens, Bacterial; Buffers; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Stability; Female; Mice; Phosphates; Protein Binding
PubMed: 23986317
DOI: 10.1128/CVI.00320-13