Natural products(NPs) are compounds that are derived from natural sources such as plants, animals, and microisms. Therapeutics has benefited from numerous drug classes derived from natural product sources. The Biophar...Natural products(NPs) are compounds that are derived from natural sources such as plants, animals, and microisms. Therapeutics has benefited from numerous drug classes derived from natural product sources. The Biopharmaceutics Drug position Classification System(BDDCS) was proposed to serve as a basis for predicting the importance of transporters and enzymes in determining drug bioavailability and disposition. It categorizes drugs into one of four biopharmaceutical classes according to their water solubility and extent of metabolism. The present paper reviews 109 drugs from natural product sources: 29% belong to class 1(high solubility, extensive metabolism), 22% to class 2(low solubility, extensive metabolism), 40% to class 3(high solubility, poor metabolism), and 9% to class 4(low solubility, poor metabolism). Herein we evaluated the characteristics of NPs in terms of BDDCS class for all 109 drugs as wells as for subsets of NPs drugs derived from plant sources as antibiotics. In the 109 NPs drugs, we piled 32 drugs from plants, 50%(16) of total in class 1, 22%(7) in class 2 and 28%(9) in class 3, none found in class 4; Meantime, the antibiotics were found 5(16%) in class 2, 22(71%) in class 3, and 4(13%) in class 4; no drug was found in class 1. Based on this classification, we anticipate BDDCS to serve as a useful adjunct in evaluating the potential characteristics of new natural products.展开更多
Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence(BE)testing for approval of immediate release(IR)solid dosage forms containing moxifloxacin hydrochloride as the API...Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence(BE)testing for approval of immediate release(IR)solid dosage forms containing moxifloxacin hydrochloride as the API manufactured by the Government Pharmaceutical Organization(GPO)are evaluated.The solubility of moxifloxacin hydrochloride determined by the shake flask method in six different pH mediums(1.2,4.5,5.4,6.4,6.8 and 7.5)was 4.988±0.1962,27.012±0.4138,21.668±0.5165,47.200±0.8095,73.438±1.7310 and 196.475±4.4624 mg/mL,respectively.The Dose/Solubility(D/S)Ratio of the highest strength(400 mg)available in the market of moxifloxacin tablets was 80.192,14.808,18.460,8.475,5.447 and 2.036 mL,respectively.展开更多
In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathema...In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathematical models and computing methods were developed. It has been used over 200 users.展开更多
To study the biopharmaceutics characteristics of paris saponin Ⅶ(PSⅦ). The solubility of PSⅦ was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSⅦ was ...To study the biopharmaceutics characteristics of paris saponin Ⅶ(PSⅦ). The solubility of PSⅦ was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSⅦ was evaluated by measuring the oil/water partition coefficient(lgP_(app)) and determining the apparent permeability coefficient(PC_(app)) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSⅦ transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSⅦ was investigated in rat. In solvents of different pH, the equilibrium solubility of PSⅦ was quite low, and the dose number of PSⅦ was larger than 1. The lgP_(app) of PSⅦ was less than 0. The apparent permeability coefficient [PC_(app)(AP-BL)] of PSⅦ in mono-layer Caco-2 cell model was less than 14.96 × 10^(-6) cm·s^(-1), and the efflux ratio of PSⅦ in mono-layer Caco-2 cell model was less than 1. The transport rate of PSⅦ in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSⅦ could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSⅦ showed low solubility and permeability,which would result in low oral bioavailability in clinic. PSⅦ belonged to Class IV compound in biopharmaceutics classification system.展开更多
Purpose: Many health systems are considered ill-equipped to adequately meet future demand. Although academic entrepreneurs and small and medium-sized enterprises (SMEs) drive health technology innovation, they often s...Purpose: Many health systems are considered ill-equipped to adequately meet future demand. Although academic entrepreneurs and small and medium-sized enterprises (SMEs) drive health technology innovation, they often suboptimally consider important market and stakeholder requirements. This can result in missed opportunities to improve health system performance, address demand-supply gaps, and achieve financial rewards. Market intelligence can provide crucial information in this regard, but scientifically sourced guidance on how to perform market research for biopharmaceutics is scarce. Our objective was, therefore, to create and provide an easily accessible biopharmaceutics market research toolbox that can be perused by academic entrepreneurs and SMEs to improve the alignment of their developments with stakeholder needs. Design: Guided by market orientation theory, we interviewed senior managers and commercialisation experts from the biopharmaceutics sector. We asked them which information they consider most relevant, and how they collect, analyse and respond to new information to align product features, positioning and stakeholder-relationship management with market needs. Findings: Our innovator toolbox consists of a high-level overview of market intelligence considerations mapped against a novel innovation framework, a stakeholder reasoning and value model, and detailed considerations (checklists) per stakeholder of biopharmaceutics interventions. Originality: We provide here the first market orientation-based overview of market intelligence considerations for the biopharmaceutics sector. Although primarily collated for academic entrepreneurs and SMEs, our innovator toolbox for the biopharmaceutics sector can help all stakeholders better understand their orientation towards markets.展开更多
In recent years,biopharmaceuticals have witnessed remarkable advancements,transforming the landscape of therapeutic interventions.Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnolo...In recent years,biopharmaceuticals have witnessed remarkable advancements,transforming the landscape of therapeutic interventions.Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes.However,their clinical success hinges significantly on overcoming drug delivery challenges related to stability,intracellular delivery,immunogenicity,and pharmacokinetic properties.Herein,we provide an overview of various marketed macromolecules,including nucleic acids,and immunotherapeutic agents such as cytokines and monoclonal antibodies,as well as other therapeutic peptides/proteins like enzymes,hormones,and coagulation factors.Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products,offering valuable insights for both scientific research and the pharmaceutical industry.展开更多
BACKGROUND Knee osteoarthritis(KOA)is a leading cause of arthritis-related morbidity.Mesenchymal stem cells(MSCs),as living biopharmaceuticals,have emerged as a potential treatment option due to their anti-inflammator...BACKGROUND Knee osteoarthritis(KOA)is a leading cause of arthritis-related morbidity.Mesenchymal stem cells(MSCs),as living biopharmaceuticals,have emerged as a potential treatment option due to their anti-inflammatory and immunomodulatory properties.AIM To compare the safety and efficacy of allogenic MSCs(^(Allo)MSCs)vs autologous MSCs(^(Auto)MSCs)in treating KOA in clinical settings.METHODS We conducted a systematic review and network meta-analysis to compare the safety and efficacy of^(Allo)MSCs vs^(Auto)MSCs in treating KOA.Our systematic search of four databases,including PubMed,Cochrane,Embase,and ClinicalTrials.gov,identified relevant randomized controlled trials(RCTs)reporting MSC-based treatment for KOA and reporting visual analog scale,Western Ontario and McMaster Universities Osteoarthritis scores,and adverse events.We assessed the methodological quality of the studies using the Cochrane Collaboration tool and calculated risk ratios(RRs)and weighted mean differences[with 95%confidence intervals(CIs)].Our statistical analyses used the R-Studio network meta-packages(version 2023.12.0).The study protocol was pre-registered on the International Prospective Register of Systematic Reviews(ID:CRD42024590866).RESULTS Nineteen RCTs involving 1216 patients with KOA met the inclusion criteria of the study.The network metaanalysis showed that^(Allo)MSCs gave a significant re-duction in visual analog scale scores by 14.91 points(95%CI:-24.52 to-5.30)vs 12.95 points with^(Auto)MSCs(95%CI:-24.42 to-1.48).For Western Ontario and McMaster Universities Osteoarthritis score,^(Allo)MSCs led to a significant reduction of 23.12 points(95%CI:-31.15 to-15.10)compared with 12.45 points using^(Auto)MSCs(95%CI:-19.31 to-5.59),thus revealing a significant improvement with^(Allo)MSCs(weighted mean difference:-10.62,95%CI:-21.23 to-0.11).Additionally,^(Auto)MSCs treatment showed a higher risk of joint-related adverse events(RR=1.39,95%CI:1.07-1.79)compared with^(Allo)MSCs(RR=1.13,95%CI:1.01-1.25).CONCLUSION^(Allo)MSCs may offer superior clinical outcomes with a lower risk of adverse events compared with^(Auto)MSCs in the treatment of KOA.However,the need for further RCTs directly comparing the two MSC types is crucial to validate this data,underscoring the importance of our findings in this field.展开更多
Objective To explore the current state of biopharmaceutical innovation in Africa by analyzing patent data related to biopharmaceutical products in African countries.Methods Based on patent data,simple descriptive stat...Objective To explore the current state of biopharmaceutical innovation in Africa by analyzing patent data related to biopharmaceutical products in African countries.Methods Based on patent data,simple descriptive statistical methods were used to analyze the trend of patent applications,the geographical distribution of patents,and the distribution of applicants in the pharmaceutical field in Africa.Besides,Excel software was used to draw charts to visualize statistical information.Results and Conclusion According to the result,a large number of patents has been granted in these countries and the number is steadily rising each year.From the figure below,we can see that the largest number of patents was granted to Morocco in 2014 with a total number of 613 patents followed by Tunisia with 315 patents,the African Intellectual Property Organization(OAPI)with 124 patents,South Africa with 106 and Mozambique with 1 patent based on data availability(IncoPat Global Patent Search Database).It was observed that,as patents were granted,the number of applications filed on this continent increased.The largest number of patents has been recorded by Morocco,Tunisia and South Africa.Patent applications in Morocco increased fast with an average annual growth of 7.3%.The increase in patent applications is due to improved research infrastructure and enhanced research activities,which shows the importance of biopharmaceutical innovation in the continent.展开更多
Yeast-based models have become a powerful platform in pharmaceutical research,offering significant potential for producing complex drugs,vaccines,and therapeutic agents.While many current drugs were discovered before ...Yeast-based models have become a powerful platform in pharmaceutical research,offering significant potential for producing complex drugs,vaccines,and therapeutic agents.While many current drugs were discovered before fully understanding their molecular mechanisms,yeast systems now provide valuable insights for drug discovery and personalized medicine.Recent advancements in genetic engineering,metabolic engineering,and synthetic biology have improved the efficiency and scalability of yeast-based production systems,enabling more sustainable and cost-effective manufacturing processes.This paper reviews the latest developments in yeast-based technologies,focusing on their use as model organisms to study disease mechanisms,identify drug targets,and develop novel therapies.We highlight key platforms such as the yeast two-hybrid system,surface display technologies,and optimized expression systems.Additionally,we explore the future integration of yeast engineering with artificial intelligence(AI),machine learning(ML),and advanced genome editing technologies like CRISPR/Cas9,which are expected to accelerate drug discovery and enable personalized therapies.Furthermore,yeast-based systems are increasingly employed in largescale drug production,vaccine development,and therapeutic protein expression,offering promising applications in clinical and industrial settings.This paper discusses the practical implications of these systems and their potential to revolutionize drug development,paving the way for safer,more effective therapies.展开更多
The biopharmaceutical industry contributes substantially to volatile organic compounds(VOCs)emissions,causing growing concerns and social developmental conflicts.This study conducted an on-site investigation of the pr...The biopharmaceutical industry contributes substantially to volatile organic compounds(VOCs)emissions,causing growing concerns and social developmental conflicts.This study conducted an on-site investigation of the process-based emission of VOCs from three biopharmaceutical enterprises.In the workshops of the three enterprises,26 VOCs were detected,which could be sorted into 4 classes:hydrocarbons,aromatic hydrocarbons,oxygen-containing compounds,and nitrogen-containing compounds.Ketones were the main components of waste gases,accounting for 44.13%-77.85%of the overall VOCs.Process-based source profiles were compiled for each process unit,with the fermentation and extraction units of tiamulin fumarate being the main source of VOC emissions.Dimethyl heptanone,vinyl acetate,diethylamine,propylene glycol methyl ether(PGME),and benzene were screened as priority pollutants through a fuzzy comprehensive evaluation system.Ground level concentration simulation results of the Gauss plume diffusion model demonstrated that the diffusivity of VOCs in the atmosphere was relatively high,indicating potential non-carcinogenic and carcinogenic risks 1.5-2 km downwind.Furthermore,the process-based formation potentials of ozone and secondary organic aerosols(SOAs)were determined and indicated that N-methyl-2-pyrrolidone,dimethyl heptanone,and PGME should be preferentially controlled to reduce the ozone formation potential,whereas the control of benzene and chlorobenzene should be prioritized to reduce the generation of SOAs.Our results provide a basis for understanding the characteristics of VOC emission by biopharmaceutical industries and their diffusion,potentially allowing the development of measures to reduce health risks and secondary pollution.展开更多
In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding ...In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.展开更多
The biopharmaceutical sector is of considerable interest during the COVID-19 pandemic.This study aims to investigate the biopharmaceutical sector using the Shenwan Industry Classification and provides insights into in...The biopharmaceutical sector is of considerable interest during the COVID-19 pandemic.This study aims to investigate the biopharmaceutical sector using the Shenwan Industry Classification and provides insights into investment strategies.We combine factor and cluster analyses to reduce data dimensions and detect their latent similarities.Specifically,the biopharmaceutical sector is divided into six categories based on second-level industry classification.It is observed that medical devices,medical services,biological products,and chemical pharmaceuticals maintained their upward tendency,while Chinese medicine and pharmaceutical commerce declined slightly.We also develop optimal investment strategies using various metrics for different investor types.展开更多
A university is a higher academic institution with a mission to educate individuals in order to help nations reach their developmental goals. It implies teaching innovative disciplines through the most advanced scient...A university is a higher academic institution with a mission to educate individuals in order to help nations reach their developmental goals. It implies teaching innovative disciplines through the most advanced scientific and pedagogical methods, in harmony with recent international standards and national needs. Some of these innovative disciplines turn out to be a valuable driving-force of the transformation in a country. An example of such transforming disciplines is the PK （pharmacokinetics） in Cuba, considered by many as exclusive of developed countries, it shows significant contributions to the current success of the local biopharmaceutical industry, and particularly to the scientific achievements of several biotechnological centers. Noteworthily, the academic activities and scientific work performed at the UH （University of Havana） and other colleges across the Island are closely related to this success. While passing through the different stages of transformation at academic institutions in the country, we discuss herein the most significant milestones in the history of the Pharmacokinetics in Cuba.展开更多
With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driv...With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships.In monoclonal antibodies,many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known.The importance of their function focuses analytical research efforts on the development of robust,accurate and fast methods to support drug development and quality control.Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however,it is not the only method for quantitative analysis of glycoform heterogeneity.In this study,ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies.While observing good comparability between the quantitative results generated,it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.展开更多
Viruses still pose a significant threat to human and animal health worldwide.In the fight against viral infections,high-purity viral stocks are needed for manufacture of safer vaccines.It is also a priority to ensure ...Viruses still pose a significant threat to human and animal health worldwide.In the fight against viral infections,high-purity viral stocks are needed for manufacture of safer vaccines.It is also a priority to ensure the viral safety of biopharmaceuticals such as blood products.Chromatography techniques are widely implemented at both academic and industrial levels in the purification of viral particles,whole viruses and virus-like particles to remove viral contaminants from biopharmaceutical products.This paper focuses on polysaccharide adsorbents,particulate resins and membrane adsorbers,used in virus purification/removal chromatography processes.Different chromatographic modes are surveyed,with particular attention to ion exchange and affinity/pseudo-affinity adsorbents among which commercially available agarose-based resins(Sepharose®)and cellulose-based membrane adsorbers(Sartobind®)occupy a dominant position.Mainly built on the development of new ligands coupled to conventional agarose/cellulose matrices,the development perspectives of polysaccharide-based chromatography media in this antiviral area are stressed in the conclusive part.展开更多
Biopharmaceuticals,such as proteins,peptides,nucleic acids and vaccines,bring about great hopes for the prevention and treatment of various diseases,but the industrialization of these products still faces challenges s...Biopharmaceuticals,such as proteins,peptides,nucleic acids and vaccines,bring about great hopes for the prevention and treatment of various diseases,but the industrialization of these products still faces challenges such as structural instability,inefficient bioactivity and low bioavailability.Ionic liquids(ILs),the marvelous solvent media with inimitable and tunable properties,may provide alternative solutions to overcome the above problems of biopharmaceutical industry.Progress has gradually been made through studies by combination of ILs with biomacromolecules.The applications involved the stabilization,protection,and delivery of biopharmaceuticals.Recent trends are being forwarded to using ILs in vaccines and nucleic acid drugs.However,challenges remain on the toxicity and safety issues.Besides,the cost of adding ILs to the benefits of biopharmaceuticals need to be considered.展开更多
Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic...Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic Classification System(BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mechanisms of baicalein in rats in vitro. Physiologically based pharmacokinetic(PBPK) model commercial software GastroPlus~(TM) was used to predict oral absorption of baicalein in vivo.Results: Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling(IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug(C_(max)) and area under the curve(AUC)fell within two times of the error of the measured results, highlighting the superior prediction of absorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evidence and provided excellent prediction for this BCS class II drug.Conclusion: BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.展开更多
The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with...The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis.Amongst them,monoclonal antibodies,anti-TNFs,and convalescent plasma appear to be effective against this disease.In addition,clinical trials are currently being conducted for viral targeting vaccines.This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.展开更多
Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full ...Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.展开更多
Microbial pathogens have always posed serious threats and challenges to human existence. Pathogenic microbes causing epidemic and pandemic outbreaks have the potential of effacing life on earth. Vaccines are used as p...Microbial pathogens have always posed serious threats and challenges to human existence. Pathogenic microbes causing epidemic and pandemic outbreaks have the potential of effacing life on earth. Vaccines are used as prophylactic as well as treatment measures against diseases and are effective in eradicating deadly pathogens. Conventional vaccines though effective, have high production costs, involve tedious purification processes and have biosafety issues, requiring time-consuming biosafety tests for commercial production. Plant-based vaccines offer several advantages over the conventional systems such as ease of production, storage, higher yields, stability and safety. The review discusses significance, advantages, comparisons, prospects and challenges or constraints in the production of plant-based vaccines and antibodies.展开更多
基金supported by China Scholarship Council(No.201208320187CSC)
文摘Natural products(NPs) are compounds that are derived from natural sources such as plants, animals, and microisms. Therapeutics has benefited from numerous drug classes derived from natural product sources. The Biopharmaceutics Drug position Classification System(BDDCS) was proposed to serve as a basis for predicting the importance of transporters and enzymes in determining drug bioavailability and disposition. It categorizes drugs into one of four biopharmaceutical classes according to their water solubility and extent of metabolism. The present paper reviews 109 drugs from natural product sources: 29% belong to class 1(high solubility, extensive metabolism), 22% to class 2(low solubility, extensive metabolism), 40% to class 3(high solubility, poor metabolism), and 9% to class 4(low solubility, poor metabolism). Herein we evaluated the characteristics of NPs in terms of BDDCS class for all 109 drugs as wells as for subsets of NPs drugs derived from plant sources as antibiotics. In the 109 NPs drugs, we piled 32 drugs from plants, 50%(16) of total in class 1, 22%(7) in class 2 and 28%(9) in class 3, none found in class 4; Meantime, the antibiotics were found 5(16%) in class 2, 22(71%) in class 3, and 4(13%) in class 4; no drug was found in class 1. Based on this classification, we anticipate BDDCS to serve as a useful adjunct in evaluating the potential characteristics of new natural products.
文摘Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence(BE)testing for approval of immediate release(IR)solid dosage forms containing moxifloxacin hydrochloride as the API manufactured by the Government Pharmaceutical Organization(GPO)are evaluated.The solubility of moxifloxacin hydrochloride determined by the shake flask method in six different pH mediums(1.2,4.5,5.4,6.4,6.8 and 7.5)was 4.988±0.1962,27.012±0.4138,21.668±0.5165,47.200±0.8095,73.438±1.7310 and 196.475±4.4624 mg/mL,respectively.The Dose/Solubility(D/S)Ratio of the highest strength(400 mg)available in the market of moxifloxacin tablets was 80.192,14.808,18.460,8.475,5.447 and 2.036 mL,respectively.
文摘In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathematical models and computing methods were developed. It has been used over 200 users.
文摘To study the biopharmaceutics characteristics of paris saponin Ⅶ(PSⅦ). The solubility of PSⅦ was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSⅦ was evaluated by measuring the oil/water partition coefficient(lgP_(app)) and determining the apparent permeability coefficient(PC_(app)) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSⅦ transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSⅦ was investigated in rat. In solvents of different pH, the equilibrium solubility of PSⅦ was quite low, and the dose number of PSⅦ was larger than 1. The lgP_(app) of PSⅦ was less than 0. The apparent permeability coefficient [PC_(app)(AP-BL)] of PSⅦ in mono-layer Caco-2 cell model was less than 14.96 × 10^(-6) cm·s^(-1), and the efflux ratio of PSⅦ in mono-layer Caco-2 cell model was less than 1. The transport rate of PSⅦ in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSⅦ could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSⅦ showed low solubility and permeability,which would result in low oral bioavailability in clinic. PSⅦ belonged to Class IV compound in biopharmaceutics classification system.
文摘Purpose: Many health systems are considered ill-equipped to adequately meet future demand. Although academic entrepreneurs and small and medium-sized enterprises (SMEs) drive health technology innovation, they often suboptimally consider important market and stakeholder requirements. This can result in missed opportunities to improve health system performance, address demand-supply gaps, and achieve financial rewards. Market intelligence can provide crucial information in this regard, but scientifically sourced guidance on how to perform market research for biopharmaceutics is scarce. Our objective was, therefore, to create and provide an easily accessible biopharmaceutics market research toolbox that can be perused by academic entrepreneurs and SMEs to improve the alignment of their developments with stakeholder needs. Design: Guided by market orientation theory, we interviewed senior managers and commercialisation experts from the biopharmaceutics sector. We asked them which information they consider most relevant, and how they collect, analyse and respond to new information to align product features, positioning and stakeholder-relationship management with market needs. Findings: Our innovator toolbox consists of a high-level overview of market intelligence considerations mapped against a novel innovation framework, a stakeholder reasoning and value model, and detailed considerations (checklists) per stakeholder of biopharmaceutics interventions. Originality: We provide here the first market orientation-based overview of market intelligence considerations for the biopharmaceutics sector. Although primarily collated for academic entrepreneurs and SMEs, our innovator toolbox for the biopharmaceutics sector can help all stakeholders better understand their orientation towards markets.
基金supported by the National Natural Science Foundation of China(Nos.82073782 and 82241002)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.21KJA320003)the Scientific Research Project of Jiangsu Commission of Health(No.LKZ2023001)。
文摘In recent years,biopharmaceuticals have witnessed remarkable advancements,transforming the landscape of therapeutic interventions.Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes.However,their clinical success hinges significantly on overcoming drug delivery challenges related to stability,intracellular delivery,immunogenicity,and pharmacokinetic properties.Herein,we provide an overview of various marketed macromolecules,including nucleic acids,and immunotherapeutic agents such as cytokines and monoclonal antibodies,as well as other therapeutic peptides/proteins like enzymes,hormones,and coagulation factors.Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products,offering valuable insights for both scientific research and the pharmaceutical industry.
文摘BACKGROUND Knee osteoarthritis(KOA)is a leading cause of arthritis-related morbidity.Mesenchymal stem cells(MSCs),as living biopharmaceuticals,have emerged as a potential treatment option due to their anti-inflammatory and immunomodulatory properties.AIM To compare the safety and efficacy of allogenic MSCs(^(Allo)MSCs)vs autologous MSCs(^(Auto)MSCs)in treating KOA in clinical settings.METHODS We conducted a systematic review and network meta-analysis to compare the safety and efficacy of^(Allo)MSCs vs^(Auto)MSCs in treating KOA.Our systematic search of four databases,including PubMed,Cochrane,Embase,and ClinicalTrials.gov,identified relevant randomized controlled trials(RCTs)reporting MSC-based treatment for KOA and reporting visual analog scale,Western Ontario and McMaster Universities Osteoarthritis scores,and adverse events.We assessed the methodological quality of the studies using the Cochrane Collaboration tool and calculated risk ratios(RRs)and weighted mean differences[with 95%confidence intervals(CIs)].Our statistical analyses used the R-Studio network meta-packages(version 2023.12.0).The study protocol was pre-registered on the International Prospective Register of Systematic Reviews(ID:CRD42024590866).RESULTS Nineteen RCTs involving 1216 patients with KOA met the inclusion criteria of the study.The network metaanalysis showed that^(Allo)MSCs gave a significant re-duction in visual analog scale scores by 14.91 points(95%CI:-24.52 to-5.30)vs 12.95 points with^(Auto)MSCs(95%CI:-24.42 to-1.48).For Western Ontario and McMaster Universities Osteoarthritis score,^(Allo)MSCs led to a significant reduction of 23.12 points(95%CI:-31.15 to-15.10)compared with 12.45 points using^(Auto)MSCs(95%CI:-19.31 to-5.59),thus revealing a significant improvement with^(Allo)MSCs(weighted mean difference:-10.62,95%CI:-21.23 to-0.11).Additionally,^(Auto)MSCs treatment showed a higher risk of joint-related adverse events(RR=1.39,95%CI:1.07-1.79)compared with^(Allo)MSCs(RR=1.13,95%CI:1.01-1.25).CONCLUSION^(Allo)MSCs may offer superior clinical outcomes with a lower risk of adverse events compared with^(Auto)MSCs in the treatment of KOA.However,the need for further RCTs directly comparing the two MSC types is crucial to validate this data,underscoring the importance of our findings in this field.
文摘Objective To explore the current state of biopharmaceutical innovation in Africa by analyzing patent data related to biopharmaceutical products in African countries.Methods Based on patent data,simple descriptive statistical methods were used to analyze the trend of patent applications,the geographical distribution of patents,and the distribution of applicants in the pharmaceutical field in Africa.Besides,Excel software was used to draw charts to visualize statistical information.Results and Conclusion According to the result,a large number of patents has been granted in these countries and the number is steadily rising each year.From the figure below,we can see that the largest number of patents was granted to Morocco in 2014 with a total number of 613 patents followed by Tunisia with 315 patents,the African Intellectual Property Organization(OAPI)with 124 patents,South Africa with 106 and Mozambique with 1 patent based on data availability(IncoPat Global Patent Search Database).It was observed that,as patents were granted,the number of applications filed on this continent increased.The largest number of patents has been recorded by Morocco,Tunisia and South Africa.Patent applications in Morocco increased fast with an average annual growth of 7.3%.The increase in patent applications is due to improved research infrastructure and enhanced research activities,which shows the importance of biopharmaceutical innovation in the continent.
基金funded by 2024 Scientific Research Project of Chongqing Medical and Pharmaceutical College(No.ygzrc2024101)Chongqing Education Commission Natural Science Foundation(No.KJQN202402821)+2 种基金Chongqing Shapingba District Science and Technology Bureau Project(No.2024071)2024 Chongqing Medical and Pharmaceutical College Innovation Research Group Project(No.ygz2024401)Chongqing Science and Health Joint Medical Research Project(No.2024SQKWLHMS051),respectively.
文摘Yeast-based models have become a powerful platform in pharmaceutical research,offering significant potential for producing complex drugs,vaccines,and therapeutic agents.While many current drugs were discovered before fully understanding their molecular mechanisms,yeast systems now provide valuable insights for drug discovery and personalized medicine.Recent advancements in genetic engineering,metabolic engineering,and synthetic biology have improved the efficiency and scalability of yeast-based production systems,enabling more sustainable and cost-effective manufacturing processes.This paper reviews the latest developments in yeast-based technologies,focusing on their use as model organisms to study disease mechanisms,identify drug targets,and develop novel therapies.We highlight key platforms such as the yeast two-hybrid system,surface display technologies,and optimized expression systems.Additionally,we explore the future integration of yeast engineering with artificial intelligence(AI),machine learning(ML),and advanced genome editing technologies like CRISPR/Cas9,which are expected to accelerate drug discovery and enable personalized therapies.Furthermore,yeast-based systems are increasingly employed in largescale drug production,vaccine development,and therapeutic protein expression,offering promising applications in clinical and industrial settings.This paper discusses the practical implications of these systems and their potential to revolutionize drug development,paving the way for safer,more effective therapies.
基金financially supported by the National Natural Science Foundation of China (No.51878650)。
文摘The biopharmaceutical industry contributes substantially to volatile organic compounds(VOCs)emissions,causing growing concerns and social developmental conflicts.This study conducted an on-site investigation of the process-based emission of VOCs from three biopharmaceutical enterprises.In the workshops of the three enterprises,26 VOCs were detected,which could be sorted into 4 classes:hydrocarbons,aromatic hydrocarbons,oxygen-containing compounds,and nitrogen-containing compounds.Ketones were the main components of waste gases,accounting for 44.13%-77.85%of the overall VOCs.Process-based source profiles were compiled for each process unit,with the fermentation and extraction units of tiamulin fumarate being the main source of VOC emissions.Dimethyl heptanone,vinyl acetate,diethylamine,propylene glycol methyl ether(PGME),and benzene were screened as priority pollutants through a fuzzy comprehensive evaluation system.Ground level concentration simulation results of the Gauss plume diffusion model demonstrated that the diffusivity of VOCs in the atmosphere was relatively high,indicating potential non-carcinogenic and carcinogenic risks 1.5-2 km downwind.Furthermore,the process-based formation potentials of ozone and secondary organic aerosols(SOAs)were determined and indicated that N-methyl-2-pyrrolidone,dimethyl heptanone,and PGME should be preferentially controlled to reduce the ozone formation potential,whereas the control of benzene and chlorobenzene should be prioritized to reduce the generation of SOAs.Our results provide a basis for understanding the characteristics of VOC emission by biopharmaceutical industries and their diffusion,potentially allowing the development of measures to reduce health risks and secondary pollution.
基金supported by the Grant for Development of New Faculty Staff,Ratchadaphiseksomphot Endowment Fund,Chula-longkorn University,Thailand(Grant No.:DNS64_047_33_003_1 to Patanachai K.Limpikirati)Grant for Development of New Scholar,Office of the Permanent Secretary,Ministry of Higher Ed-ucation,Science,Research and Innovation,Thailand(Grant No.:RGNS64_012 to Patanachai K.Limpikirati).
文摘In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.
基金XJTLU Postgraduate Research Scholarship-PGRS2012016.
文摘The biopharmaceutical sector is of considerable interest during the COVID-19 pandemic.This study aims to investigate the biopharmaceutical sector using the Shenwan Industry Classification and provides insights into investment strategies.We combine factor and cluster analyses to reduce data dimensions and detect their latent similarities.Specifically,the biopharmaceutical sector is divided into six categories based on second-level industry classification.It is observed that medical devices,medical services,biological products,and chemical pharmaceuticals maintained their upward tendency,while Chinese medicine and pharmaceutical commerce declined slightly.We also develop optimal investment strategies using various metrics for different investor types.
文摘A university is a higher academic institution with a mission to educate individuals in order to help nations reach their developmental goals. It implies teaching innovative disciplines through the most advanced scientific and pedagogical methods, in harmony with recent international standards and national needs. Some of these innovative disciplines turn out to be a valuable driving-force of the transformation in a country. An example of such transforming disciplines is the PK （pharmacokinetics） in Cuba, considered by many as exclusive of developed countries, it shows significant contributions to the current success of the local biopharmaceutical industry, and particularly to the scientific achievements of several biotechnological centers. Noteworthily, the academic activities and scientific work performed at the UH （University of Havana） and other colleges across the Island are closely related to this success. While passing through the different stages of transformation at academic institutions in the country, we discuss herein the most significant milestones in the history of the Pharmacokinetics in Cuba.
文摘With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships.In monoclonal antibodies,many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known.The importance of their function focuses analytical research efforts on the development of robust,accurate and fast methods to support drug development and quality control.Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however,it is not the only method for quantitative analysis of glycoform heterogeneity.In this study,ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies.While observing good comparability between the quantitative results generated,it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.
文摘Viruses still pose a significant threat to human and animal health worldwide.In the fight against viral infections,high-purity viral stocks are needed for manufacture of safer vaccines.It is also a priority to ensure the viral safety of biopharmaceuticals such as blood products.Chromatography techniques are widely implemented at both academic and industrial levels in the purification of viral particles,whole viruses and virus-like particles to remove viral contaminants from biopharmaceutical products.This paper focuses on polysaccharide adsorbents,particulate resins and membrane adsorbers,used in virus purification/removal chromatography processes.Different chromatographic modes are surveyed,with particular attention to ion exchange and affinity/pseudo-affinity adsorbents among which commercially available agarose-based resins(Sepharose®)and cellulose-based membrane adsorbers(Sartobind®)occupy a dominant position.Mainly built on the development of new ligands coupled to conventional agarose/cellulose matrices,the development perspectives of polysaccharide-based chromatography media in this antiviral area are stressed in the conclusive part.
基金The authors are thankful for the financial support from the National Natural Science Foundation of China(Nos.21808226,31970872,and 21821005).
文摘Biopharmaceuticals,such as proteins,peptides,nucleic acids and vaccines,bring about great hopes for the prevention and treatment of various diseases,but the industrialization of these products still faces challenges such as structural instability,inefficient bioactivity and low bioavailability.Ionic liquids(ILs),the marvelous solvent media with inimitable and tunable properties,may provide alternative solutions to overcome the above problems of biopharmaceutical industry.Progress has gradually been made through studies by combination of ILs with biomacromolecules.The applications involved the stabilization,protection,and delivery of biopharmaceuticals.Recent trends are being forwarded to using ILs in vaccines and nucleic acid drugs.However,challenges remain on the toxicity and safety issues.Besides,the cost of adding ILs to the benefits of biopharmaceuticals need to be considered.
基金supported by the National Natural Science Foundation of China (81473362)。
文摘Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.Methods: The Biopharmaceutic Classification System(BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mechanisms of baicalein in rats in vitro. Physiologically based pharmacokinetic(PBPK) model commercial software GastroPlus~(TM) was used to predict oral absorption of baicalein in vivo.Results: Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling(IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug(C_(max)) and area under the curve(AUC)fell within two times of the error of the measured results, highlighting the superior prediction of absorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evidence and provided excellent prediction for this BCS class II drug.Conclusion: BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.
基金financial support from the Food and Drug Safety Research Center at Tabriz University of Medical Sciences(Grant No.66317).
文摘The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis.Amongst them,monoclonal antibodies,anti-TNFs,and convalescent plasma appear to be effective against this disease.In addition,clinical trials are currently being conducted for viral targeting vaccines.This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.
基金funded by Project FIS:PI10/00201 (Instituto Carlos III, Ministerio de Economía y Competitividad, Spain)partially supported by European Regional Development Funds (ERDF)
文摘Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.
文摘Microbial pathogens have always posed serious threats and challenges to human existence. Pathogenic microbes causing epidemic and pandemic outbreaks have the potential of effacing life on earth. Vaccines are used as prophylactic as well as treatment measures against diseases and are effective in eradicating deadly pathogens. Conventional vaccines though effective, have high production costs, involve tedious purification processes and have biosafety issues, requiring time-consuming biosafety tests for commercial production. Plant-based vaccines offer several advantages over the conventional systems such as ease of production, storage, higher yields, stability and safety. The review discusses significance, advantages, comparisons, prospects and challenges or constraints in the production of plant-based vaccines and antibodies.
