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1.
Artigo em Chinês | WPRIM | ID: wpr-1031457

RESUMO

The dosage, dose and administration method of decoctions are important factors affecting the efficacy of prescriptions. By analyzing 35 decoction formulas from the Ming and Qing dynasties within the Catalogue of Ancient Classic Famous Formulas (First Batch), it was found that the average dosage was equivalent to about 65 g, of which 71.4% (25/35) of the prescriptions had a dosage ≤60 g. And among them, the dosage of decoctions in the Ming dynasty was significantly smaller than that in the Qing dynasty. Considering the characteristics of formulas in Song dynasty, it is believed that decoctions in Ming and Qing dynasties were influenced by the popular use of decoctions during the Song, Jin, and Yuan dynasties. Some decoctions recorded a dosage of one dose instead of one day, which was more evident in the Ming dynasty. However, by the Qing dynasty, the usage of prescriptions with a dosage of one day gradually became more common. Therefore, in the practical research and application of classic famous formulas from the Ming and Qing dynasties, it is advised to pay attention to the difference between the dosage, one dose and the daily dosage. It is necessary to determine whether to double the dosage of the original formula based on the actual use, in order to ensure the clinical efficacy.

2.
China Pharmacy ; (12): 1291-1295, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1031702

RESUMO

OBJECTIVE To investigate the marketing status, general characteristics, and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog, the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation, National Medical Products Administration and Yaozhi.com, and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31, 2022, only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China, and 79 rare disease drugs have been approved. Among them, 46.84% of the drugs are domestic drugs, 88.61% of the drugs are approved for use in both adults and children; 67.09% are chemicals and 59.49% are injections. According to the ATC classification, Category A (digestive system drugs) is the most, accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021, with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year, according to the ATC classification, the number of Category L (antineoplastics and immune inhibitors) will be the largest in 2021, being 5. By dosage form, oral medicines were marketed in the largest number in 2022, and injectable medicines in 2021. CONCLUSIONS In recent years, the number of approved rare disease drugs in China has been continuously increasing, but it is still far from meeting the needs of patients, and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs, and promote the import and replication of rare disease drugs.

3.
China Pharmacy ; (12): 1291-1295, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1031724

RESUMO

OBJECTIVE To investigate the marketing status, general characteristics, and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog, the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation, National Medical Products Administration and Yaozhi.com, and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31, 2022, only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China, and 79 rare disease drugs have been approved. Among them, 46.84% of the drugs are domestic drugs, 88.61% of the drugs are approved for use in both adults and children; 67.09% are chemicals and 59.49% are injections. According to the ATC classification, Category A (digestive system drugs) is the most, accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021, with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year, according to the ATC classification, the number of Category L (antineoplastics and immune inhibitors) will be the largest in 2021, being 5. By dosage form, oral medicines were marketed in the largest number in 2022, and injectable medicines in 2021. CONCLUSIONS In recent years, the number of approved rare disease drugs in China has been continuously increasing, but it is still far from meeting the needs of patients, and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs, and promote the import and replication of rare disease drugs.

4.
Chinese Journal of Biologicals ; (12): 866-872, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1039280

RESUMO

@#Objective To compare and analyze two methods for determination of vaccine particle content in freeze-dried human rabies vaccine(Vero cells)bulk and final bulk,and to provide experimental basis for establishing standard detection method for particle content and purity of rabies vaccine products.Methods The samples were subjected to vaccine particle cracking,BCA quantification,and size exclusion chromatograghy-high performance liquid chromatography(SEC-HPLC)analysis. BCA-SEC relative area method and BCA-SEC vaccine particle standard curve method were used to detect the total protein concentration of the bulk and final bulk,separately,and the content of vaccine particles was quantitatively analy-zed. Finally,the detection results of the two methods were compared and analyzed.Results The content of vaccine particles in freeze-dried human rabies vaccine bulk was determined to be within 256-305 μg/mL by the two methods,with an average value of 267-285 μg/mL,and the relative standard deviations(RSDs)ranged from 5. 8% to 10. 2%,with good consistency between two methods. The content of vaccine particles in freeze-dried human rabies vaccine final bulk was determined to be in the range of 149-169 μg/mL by the two methods,with an average value of 152-164 μg/mL,and the two methods showed the RSDs between 0. 9%-4. 7% with good consistency.Conclusion The measured value by BCA-SEC standard curve method deviates less from the expected value and is closer to the actual situation of samples,so it is recommended to use this method as a reference for enterprises.

5.
Rev. colomb. biotecnol ; 25(1)jun. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1535723

RESUMO

Se evaluó la biodegradación de polietilenglicol de peso molecular 400 - PEG 400 con el consorcio Pseudomonas sp. y Rhizobium trifolii en reactores en Batch; para determinar las condiciones óptimas de operación del reactor se preparó medio con sales mínimas esenciales suplementado con peptonaCSMEP; en estos medios se estimó el comportamiento del consorcio con condiciones de temperatura entre 15-37°C, pH en un rango de 5-9 y concentración de PEG 400 del .1-2%. Con los resultados obtenidos en estos ensayos previos se ensamblaron tres reactores en Batch - BK. Se analizaron 14 muestras del contenido de cada uno de los reactores durante 20 días para medir la biodegradación del PEG 400 usando demanda química de oxígeno - DQO en sistema de digestión cerrado. Se obtuvo una disminución de hasta el 98.5% del poliéter, lo que mostró que la simbiosis fue efectiva para alcanzar una remoción importante del contaminante.


The biodegradation of polyethylene glycol of molecular weight 400 - PEG 400 was evaluated with the consortium Pseudomonas sp. and Rhizobium trifolii in Batch reactors. To determine the optimal operating conditions of the reactor, a medium with minimum essential salts supplemented with CSMEP peptone was prepared; In these media, the behavior of the consortium was estimated with temperature conditions between 15-37°C, pH in a range of 5-9 and PEG 400 concentration of .1-2%. With the results obtained in these previous tests, three Batch - BK reactors were assembled. 14 samples of the contents of each one of the reactors were analyzed during 20 days to measure the biodegradation of PEG 400 using chemical oxygen demand - COD in a closed digestion system. A decrease of up to 98.5% of the polyether was obtained, which showed that the symbiosis was effective to achieve an important removal of the contaminant.

6.
Artigo em Chinês | WPRIM | ID: wpr-969997

RESUMO

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.


Assuntos
Moxibustão , Terapia por Acupuntura , Instituições Acadêmicas
7.
Artigo em Chinês | WPRIM | ID: wpr-1008908

RESUMO

In order to fully explore the neural oscillatory coupling characteristics of patients with mild cognitive impairment (MCI), this paper analyzed and compared the strength of the coupling characteristics for 28 MCI patients and 21 normal subjects under six different-frequency combinations. The results showed that the difference in the global phase synchronization index of cross-frequency coupling under δ-θ rhythm combination was statistically significant in the MCI group compared with the normal control group ( P = 0.025, d = 0.398). To further validate this coupling feature, this paper proposed an optimized convolutional neural network model that incorporated a time-frequency data enhancement module and batch normalization layers to prevent overfitting while enhancing the robustness of the model. Based on this optimized model, with the phase locking value matrix of δ-θ rhythm combination as the single input feature, the diagnostic accuracy of MCI patients was (95.49 ± 4.15)%, sensitivity and specificity were (93.71 ± 7.21)% and (97.50 ± 5.34)%, respectively. The results showed that the characteristics of the phase locking value matrix under the combination of δ-θ rhythms can adequately reflect the cognitive status of MCI patients, which is helpful to assist the diagnosis of MCI.


Assuntos
Humanos , Eletroencefalografia/métodos , Disfunção Cognitiva/diagnóstico , Redes Neurais de Computação , Sensibilidade e Especificidade
8.
China Pharmacy ; (12): 1142-1146, 2023.
Artigo em Chinês | WPRIM | ID: wpr-972962

RESUMO

OBJECTIVE To establish a drug batch number traceability management mode in intelligent anesthesia pharmacy of operating room, improve the management level of batch number traceability in anesthesia pharmacy of operating room and ensure the safety of surgical medication. METHODS The problems encountered in the application of batch number traceability management mode in intelligent anesthesia pharmacy of operating room were analyzed to implement the optimization measure and summarize the optimization effect. RESULTS In view of the incompatibility of multiple batch numbers on the dosing track, the insufficient number of drugs in the automated dispensing cabinet, the long replenishment time, the low stability of the automated dispensing cabinet, and the tedious management of drugs with a near-expiration period, the following measures were implemented, including changing the minimum unit of dosing, adjusting the drug base number and surgery schedule, optimizing the supplementary drug delivery order, repairing dosing tracks of the automated dispensing cabinet, adding the batch number correction function, improving the screening function of drugs with a near-expiration period, and configuring the automated dispensing cabinet in the recovery room. It realized the coexistence of multiple batch numbers on the dosing track, the sufficient number of drugs in the automated dispensing cabinet, the shortening of the replenishment time, the improvement in the stability of the automated dispensing cabinet, and the efficient management of drugs with a near-expiration period. CONCLUSIONS The batch number traceability management mode is established in intelligent anesthesia pharmacy of operating room in our hospital, which improves the system function module, optimizes the work process, increases the stability of the automated dispensing cabinet, improves the work efficiency, and realizes the refined management of surgical medication.

9.
Chinese Journal of Biotechnology ; (12): 796-806, 2022.
Artigo em Chinês | WPRIM | ID: wpr-927745

RESUMO

Ergothioneine (ERG) is a natural antioxidant that has been widely used in the fields of food, medicine and cosmetics. Compared with traditional plant extraction and chemical synthesis approaches, microbial synthesis of ergothioneine has many advantages, such as the short production cycle and low cost, and thus has attracted intensive attention. In order to engineer an ergothioneine high-yielding Escherichia coli strain, the ergothioneine synthesis gene cluster egtABCDE from Mycobacterium smegmatis and egt1 from Schizosaccharomyces pombe were introduced into E. coli BL21(DE3) to generate a strain E1-A1 harboring the ergothioneine biosynthesis pathway. As a result, (95.58±3.2) mg/L ergothioneine was produced in flask cultures. To further increase ergothioneine yield, the relevant enzymes for biosynthesis of histidine, methionine, and cysteine, the three precursor amino acids of ergothioneine, were overexpressed. Individual overexpression of serAT410STOP and thrA resulted in an ergothioneine titer of (134.83±4.22) mg/L and (130.26±3.34) mg/L, respectively, while co-overexpression of serAT410STOP and thrA increased the production of ergothioneine to (144.97±5.40) mg/L. Eventually, by adopting a fed-batch fermentation strategy in 3 L fermenter, the optimized strain E1-A1-thrA-serA* produced 548.75 mg/L and 710.53 mg/L ergothioneine in glucose inorganic salt medium and rich medium, respectively.


Assuntos
Meios de Cultura , Ergotioneína/metabolismo , Escherichia coli/metabolismo , Fermentação , Histidina/metabolismo , Engenharia Metabólica
10.
Chinese Journal of Biotechnology ; (12): 868-881, 2022.
Artigo em Chinês | WPRIM | ID: wpr-927750

RESUMO

Ectoine is an amino acid derivative and an important natural product in halophilic microorganisms. It plays an important role in protecting cells and stabilizing biological macromolecules, and can be widely used in biomedical fields such as drug preparation adjuvants, organ transplantation and preservation, skin wound repair and cosmetics. Due to the medical value and commercial market demand of ectoine, this article summarized the recent advances in the microbial production of ectoine, including the mutation and breeding of hyper-producing strains, construction of genetically and metabolically engineered strains, optimization of fermentation processes, and extraction and purification processes. The application of multi-omics technologies and computational biology to develop an ectoine producing cell factory was prospected, with the aim to provide a reference for ectoine overproduction.


Assuntos
Diamino Aminoácidos/metabolismo , Fermentação
11.
Artigo em Chinês | WPRIM | ID: wpr-1004059

RESUMO

【Objective】 To compare the effectiveness of the old mode of blood isolation and batch release (the old mode) and the new mode in Chengdu, so as to provide basis for optimizing working strategy. 【Methods】 1) The blood testing report was released one by one in the old mode but released uniformly in accordance with the blood batches classified by blood storage and supply department in the new mode. 2) In the old mode, apheresis platelet samples were detected by serological testing first and nucleic acid testing(NAT) later, and whole blood samples were reasonably arranged according to blood inventory and detection workload. In the new mode, platelets samples collected within our center headquarters were detected by serological test and NAT simultaneously, while those collected outside the center complied with the old strategy. As for whole blood, the same batch samples classified by blood storage and supply department should be arranged to the detection line with the fewest samples.3) The turnaround time(TAT) in the laboratory (referred to as sample TAT) and the TAT in the blood to-detect stock (referred to as blood TAT) in two phases(year 2016 vs 2018, pre- and post- the new mode), involving 164 748 and 179 488 blood samples, were compared by SPSS25.0 software. The constituent ratio of the TATs were compared with Chi-square test, and the difference of blood TAT between old and new mode were compared with Mann-Whitney U test. 【Results】 1) Significant difference was noticed in constituent ratio of TATs between old and new mode (P<0.05). 2)The blood TATof apheresis platelets using the new mode was 0.95(QR: 0.22)days, with the median 0.20 days shorter than that the old mode.. The blood TAT of whole blood in the new mode was 3.77 (QR: 1.99) days, with the median 0.90 days shorter than that in the old mode, and the difference was statistically significant (P<0.05). 【Conclusion】 Compared with the old mode, the new mode showed the following advantages: 1) It can realize the unified issuing of testing reports of blood with the same batch, contribute to the early discovery of errors that occurred during blood donation process, and located the errors wihin intra-batches for investigation. 2) It can advance the issuing of blood testing reports of the same batch. 3) It can make the flow of samples and blood with the same batch between different departments more standardized and orderly, and optimize the process of blood sorting thus shortening blood TAT. 4) It can realize the counting and checking of samples, within the same batch, at different states, so as to minimize the error issuing of unqualified blood and to-detect blood, and is more conducive to ensure the quality, safety and timely supply of blood.

12.
Artigo em Chinês | WPRIM | ID: wpr-1004290

RESUMO

【Objective】 To establish a method for batch weighing blood components intelligently and accurately. 【Methods】 Virus inactivated plasma was used as weighing samples. The traditional electric scale and cryoprecipitation preparation instrument were used to weigh plasma with five specifications. The consistency of the weighing results by the two methods was statistically analyzed. Two groups of virus inactivated plasma with basically the same number of bags were randomly selected, and weighted by the same group of staff using these two equipment, the time for weighing and the time from weighing to registering were calculated statistically. 【Results】 227 bags of plasma were weighed in batches by the two methods, and statistical analysis showed no significant difference in standardized blood volume. There was no significant difference in plasma weighing time (71/68)by the same staff, weighing basically the same number of bags. However, the time difference from weighing to registering was statistically significant, as the new method was 2.65 s shorter than the traditional one (P<0.05). 【Conclusion】 The new method is accurate for batch weighing, and can realize the informatization and intellectualization of blood weighting. The time consumed from weighing to registration was improved by the new method, but not in time for weighing.

13.
São Paulo; s.n; s.n; 2022. 221 p. tab, graf.
Tese em Português | LILACS | ID: biblio-1392194

RESUMO

Para que os fármacos possam ser comercializados economicamente, a sua escala de produção deve ser aumentada para atender à demanda do mercado. Atualmente, a maior parte dos fármacos são sintetizados em processos batelada que possuem limitações quanto à eficiência de mistura, temperatura e pressão. O uso de microrreatores surge como alternativa na indústria químico-farmacêutica, aumentando a eficiência dos processos de maneira segura. Ferramentas utilizadas no segmento computacional multidisciplinar teórico, como o DFT (Density Functional Theory), podem prever e compreender o comportamento das reações químicas, podendo ter grande utilidade na síntese de novos fármacos economizando tempo, investimento e reduzindo a geração de resíduos. A diabetes mellitus é uma doença de caráter epidêmico, que a cada ano vem aumentando o número de casos. O emprego de fármacos derivados das glitazonas no tratamento de diabetes mellitus tipo 2 é recomendado devido ao excelente controle glicêmico que esta classe de fármacos oferece. Neste trabalho, foi sintetizada a Rosiglitazona, um fármaco derivado das glitazonas, que auxilia no tratamento da diabetes mellitus tipo 2, sendo estudadas duas rotas de síntese distintas, que foram otimizadas com o intuito de maximizar o rendimento de seus intermediários, obtendo a Rosiglitazona com pureza de cerca de 94%. Foi realizada, para os intermediários, aqui denominados, 1R, 2R2 e 3R2 a síntese one-pot e para os intermediários 1R, 2R1 e 3R2 foi realizada a transposição do processo usual em batelada para fluxo contínuo no microrreator, com rendimentos de até 93%. Com o auxílio da química quântica computacional, a reação de síntese do intermediário 1R, foi elucidada teoricamente e determinadas as grandezas termodinâmicas (ΔH‡, ΔG‡ e ΔS‡) no estado de transição, que foram comparadas com os valores experimentais, sendo constatada uma boa concordância, com desvio máximo de 14%


In order for drugs to be commercialized economically, their production scale must be increased to meet market demand. Currently, most drugs are synthesized in batch processes that have limitations in terms of mixing efficiency, temperature and pressure. The use of microreactors appears as an alternative in the chemical-pharmaceutical industry, increasing the efficiency of the synthesis processes in a safe way. Tools used in the theoretical multidisciplinary computational segment, such as DFT (Density Functional Theory), can predict and understand the behavior of chemical reactions, and can be very useful in the synthesis of new drugs, saving time, investment and reducing waste generation. Diabetes mellitus is an epidemic disease that has been increasing the number of cases every year. The use of drugs derived from glitazones in the treatment of type 2 diabetes mellitus is recommended due to the excellent glycemic control that this class of drugs offers. In this work, Rosiglitazone, a drug derived from glitazones, which helps in the treatment of type 2 diabetes mellitus, was synthesized. Two different synthetic routes were studied and optimized in order to maximize the yield of its intermediates, obtaining Rosiglitazone with purity of about 94%. One-pot synthesis was performed to 1R, 2R2 and 3R2 intermediates, and the transposition from the usual batch process to continuous flow in microreactor was performed to 1R, 2R1 and 3R2 intermediates, with yields of up to 93%. With the aid of computational quantum chemistry, the intermediate 1R synthesis reaction was theoretically elucidated and the thermodynamic properties were determined (ΔH‡, ΔG‡ and ΔS‡) in the transition state, which were compared with the experimental results, obtaining good agreement, with a maximum deviation of 14%


Assuntos
Preparações Farmacêuticas/provisão & distribuição , Indústria Farmacêutica/organização & administração , Rosiglitazona/análise , Biofarmácia/classificação , Reações Químicas , Diabetes Mellitus Tipo 2/patologia , Teoria da Densidade Funcional , Controle Glicêmico/instrumentação , Investimentos em Saúde/classificação
14.
São Paulo; s.n; s.n; 2022. 221 p. tab, graf.
Tese em Português | LILACS | ID: biblio-1390804

RESUMO

Para que os fármacos possam ser comercializados economicamente, a sua escala de produção deve ser aumentada para atender à demanda do mercado. Atualmente, a maior parte dos fármacos são sintetizados em processos batelada que possuem limitações quanto à eficiência de mistura, temperatura e pressão. O uso de microrreatores surge como alternativa na indústria químico-farmacêutica, aumentando a eficiência dos processos de maneira segura. Ferramentas utilizadas no segmento computacional multidisciplinar teórico, como o DFT (Density Functional Theory), podem prever e compreender o comportamento das reações químicas, podendo ter grande utilidade na síntese de novos fármacos economizando tempo, investimento e reduzindo a geração de resíduos. A diabetes mellitus é uma doença de caráter epidêmico, que a cada ano vem aumentando o número de casos. O emprego de fármacos derivados das glitazonas no tratamento de diabetes mellitus tipo 2 é recomendado devido ao excelente controle glicêmico que esta classe de fármacos oferece. Neste trabalho, foi sintetizada a Rosiglitazona, um fármaco derivado das glitazonas, que auxilia no tratamento da diabetes mellitus tipo 2, sendo estudadas duas rotas de síntese distintas, que foram otimizadas com o intuito de maximizar o rendimento de seus intermediários, obtendo a Rosiglitazona com pureza de cerca de 94%. Foi realizada, para os intermediários, aqui denominados, 1R, 2R2 e 3R2 a síntese one-pot e para os intermediários 1R, 2R1 e 3R2 foi realizada a transposição do processo usual em batelada para fluxo contínuo no microrreator, com rendimentos de até 93%. Com o auxílio da química quântica computacional, a reação de síntese do intermediário 1R, foi elucidada teoricamente e determinadas as grandezas termodinâmicas (ΔH‡, ΔG‡ e ΔS‡) no estado de transição, que foram comparadas com os valores experimentais, sendo constatada uma boa concordância, com desvio máximo de 14%


In order for drugs to be commercialized economically, their production scale must be increased to meet market demand. Currently, most drugs are synthesized in batch processes that have limitations in terms of mixing efficiency, temperature and pressure. The use of microreactors appears as an alternative in the chemical-pharmaceutical industry, increasing the efficiency of the synthesis processes in a safe way. Tools used in the theoretical multidisciplinary computational segment, such as DFT (Density Functional Theory), can predict and understand the behavior of chemical reactions, and can be very useful in the synthesis of new drugs, saving time, investment and reducing waste generation. Diabetes mellitus is an epidemic disease that has been increasing the number of cases every year. The use of drugs derived from glitazones in the treatment of type 2 diabetes mellitus is recommended due to the excellent glycemic control that this class of drugs offers. In this work, Rosiglitazone, a drug derived from glitazones, which helps in the treatment of type 2 diabetes mellitus, was synthesized. Two different synthetic routes were studied and optimized in order to maximize the yield of its intermediates, obtaining Rosiglitazone with purity of about 94%. One-pot synthesis was performed to 1R, 2R2 and 3R2 intermediates, and the transposition from the usual batch process to continuous flow in microreactor was performed to 1R, 2R1 and 3R2 intermediates, with yields of up to 93%. With the aid of computational quantum chemistry, the intermediate 1R synthesis reaction was theoretically elucidated and the thermodynamic properties were determined (ΔH‡, ΔG‡ and ΔS‡) in the transition state, which were compared with the experimental results, obtaining good agreement, with a maximum deviation of 14%.


Assuntos
Capilares/metabolismo , Crescimento e Desenvolvimento , Rosiglitazona/análise , Teoria da Densidade Funcional , Diabetes Mellitus/patologia , Indústria Farmacêutica/classificação , Medicamentos de Referência , Controle Glicêmico/classificação
15.
Electron. j. biotechnol ; 54: 8.6-93, nov.2021. ilus, graf
Artigo em Inglês | LILACS | ID: biblio-1511205

RESUMO

BACKGROUND Planctomycetes is a phylum of biofilm-forming bacteria with numerous biosynthetic gene clusters, offering a promising source of new bioactive secondary metabolites. However, the current generation of chemically defined media achieves only low biomass yields, hindering research on these species. We therefore developed a chemically defined medium for the model organism Planctopirus limnophila to increase biomass production. RESULTS We found that P. limnophila grows best with a 10 mM sodium phosphate buffer. The replacement of complex nitrogen sources with defined amino acid solutions did not inhibit growth. Screening for vitamin requirements revealed that only cyanocobalamin (B12) is needed for growth. We used response surface methodology to optimize the medium, resulting in concentrations of 10 g/L glucose, 34 mL/L Hutner's basal salts, 23.18 mM KNO3, 2.318 mM NH4Cl and 0.02 mg/L cyanocobalamin. The analysis of amino acid consumption allowed us to develop a customized amino acid solution lacking six of the amino acids present in Aminoplasmal 10%. Fed-batch cultivation in a bioreactor using the optimized medium achieved a final DOD600 of 46.8 ± 0.5 after 108 h, corresponding to a cell dry weight of 13.6 ± 0.7 g/L. CONCLUSIONS The optimized chemically defined medium allowed us to produce larger amounts of biomass more quickly than reported in earlier studies. Further research should focus on triggering P. limnophila biofilm formation to activate the gene clusters responsible for secondary metabolism


Assuntos
Planctomycetales/metabolismo , Planctomycetales/química , Aminoácidos/química , Biomassa , Planctomycetales/crescimento & desenvolvimento , Aminoácidos/metabolismo
16.
Eng. sanit. ambient ; 26(4): 603-612, ago. 2021. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1339851

RESUMO

RESUMO Neste estudo, foram obtidas as cinéticas e isotermas de adsorção do fenol presentes em efluentes sintéticos em reator batelada e coluna de leito fixo, utilizando como adsorvente carvão ativado de casca de coco. O objetivo foi a obtenção dos parâmetros cinéticos e de equilíbrio do processo para simular diferentes condições operacionais em uma coluna de adsorção em leito fixo. Foram avaliadas a influência do pH, a massa de adsorvente, a concentração inicial de fenol e três diferentes temperaturas para os testes em reator batelada. Foi possível trabalhar no pH natural da solução e o aumento da temperatura indicou adsorção exotérmica, favorável e espontânea. Os dois modelos de isoterma (Langmuir e Freundlich) representaram bem os dados experimentais (R2 ≈ 0,9). Valores aproximados de capacidade máxima de adsorção foram encontrados para o reator batelada e para a coluna de leito fixo (qmáx = 41,69 mg.g-1 para o reator batelada e qmáx = 41,98 mg.g-1 para a coluna de leito fixo). O método de Volumes Finitos foi utilizado na discretização das equações matemáticas e um algoritmo computacional foi implementado em linguagem FORTRAN. O código computacional foi validado com dados experimentais deste trabalho (erro médio de 13%), podendo-se assim simular diferentes condições operacionais do sistema de adsorção em coluna de leito fixo com vista a futuras aplicações industriais.


ABSTRACT In this study, the kinetics and adsorption isotherms of phenol present in synthetic effluents were obtained in a batch reactor and fixed bed column, using adsorbent coconut shell activated carbon. The objective was to obtain the kinetic and equilibrium parameters of the process to simulate different operating conditions in a fixed bed adsorption column. The influence of the pH, adsorbent mass, initial phenol concentration, and three different temperatures for the batch reactor tests were evaluated. It was possible to work on the natural pH of the solution and the temperature increase indicated exothermic, favorable, and spontaneous adsorption. Both isotherm models (Langmuir and Freundlich) represented the experimental data (R2 ≈ 0.9). Approximate values of maximum adsorption capacity were found for the batch reactor and for the fixed bed column (qmax = 41.69 mg g-1 for the batch reactor and qmax = 41.98 mg g-1 for the fixed bed column). The Finite Volume method was used in the discretization of the mathematical equations and a computational algorithm was implemented in FORTRAN programming language. The computational code was validated with experimental data of this work (mean error of 13%) and it was possible to simulate different operational conditions of the fixed bed column adsorption system for future industrial applications.

17.
Electron. j. biotechnol ; 50: 45-52, Mar. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1292328

RESUMO

BACKGROUND: Lawsonia intracellularis remains a problem for the swine industry worldwide. Previously, we designed and obtained a vaccine candidate against this pathogen based on the chimeric proteins: OMP1c, OMP2c, and INVASc. These proteins formed inclusion bodies when expressed in E. coli, which induced humoral and cellular immune responses in vaccinated pigs. Also, protection was demonstrated after the challenge. In this study, we established a production process to increase the yields of the three antigens as a vaccine candidate. RESULTS: Batch and fed-batch fermentations were evaluated in different culture conditions using a 2 L bioreactor. A fed-batch culture with a modified Terrific broth medium containing glucose instead of glycerol, and induced with 0.75 mM IPTG at 8 h of culture (11 g/L of biomass) raised the volumetric yield to 627.1 mg/L. Under these culture conditions, plasmid-bearing cells increased by 10% at the induction time. High efficiency in cell disruption was obtained at passage six using a high-pressure homogenizer and a bead mill. The total antigen recovery was 64% (400 mg/L), with a purity degree of 70%. The antigens retained their immunogenicity in pigs, inducing high antibody titers. CONCLUSIONS: Considering that the antigen production process allowed an increment of more than 70-fold, this methodology constitutes a crucial step in the production of this vaccine candidate against L. intracellularis.


Assuntos
Animais , Doenças dos Suínos/imunologia , Vacinas Bacterianas/imunologia , Lawsonia (Bactéria)/imunologia , Infecções por Desulfovibrionaceae/prevenção & controle , Suínos , Doenças dos Suínos/prevenção & controle , Vacinas Bacterianas/administração & dosagem , Vacinas Sintéticas , Sobrevivência Celular , Vacinação , Fermentação , Técnicas de Cultura Celular por Lotes , Imunidade
18.
Chinese Journal of Biotechnology ; (12): 3334-3347, 2021.
Artigo em Chinês | WPRIM | ID: wpr-921429

RESUMO

Cordycepin is the key active component of medicinal fungus Cordyceps militaris, and it shows multiple functional activities such as anti-tumor and anti-virus. Cordycepin was conventionally produced by liquid fermentation of C. militaris, but the long production cycle and the low productivity constrained its development and application. In this study, two key genes for cordycepin biosynthesis (ScCNS1 and ScCNS2) were introduced into Saccharomyces cerevisiae S288C, producing 67.32 mg/L cordycepin at 240 h. Analysis of gene expression profiles indicated that ZWF1, PRS4, ADE4, ScCNS1 and ScCNS2 which encode enzymes involved in pentose phosphate pathway, purine metabolism and cordycepin biosynthesis pathway, were significantly up-regulated in the late phage of fermentation. Optimization of fermentation medium determined that 50 g/L initial glucose followed by feeding, supplemented with 5 mmol/L Cu²⁺ and 1.0 g/L adenine were the best condition. Fed-batch fermentation using the engineered yeast in a 5 L stirred fermenter produced 137.27 mg/L cordycepin at 144 h, with a productivity up to 0.95 mg/(L·h) reached, which was 240% higher than that of the control.


Assuntos
Cordyceps , Meios de Cultura , Desoxiadenosinas , Saccharomyces cerevisiae/genética
19.
Artigo em Chinês | WPRIM | ID: wpr-921703

RESUMO

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) β-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 μm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.


Assuntos
Cromatografia Capilar Eletrocinética Micelar , Medicamentos de Ervas Chinesas , Micelas , Controle de Qualidade , Saponinas
20.
China Pharmacy ; (12): 247-253, 2021.
Artigo em Chinês | WPRIM | ID: wpr-862652

RESUMO

OBJECTIVE:To investigate the effects of the third batc h of Shanghai drug quantity purchasing and national “4+7” drug quantity purchasing in a Shanghai hospital and its impact on the use of statins. METHODS :Consumption amount (tablets) and sum of statins were collected from information system of this hospital before (Feb. 10th-Aug. 31th,2018)and after (Sept. 1th,2018-Mar. 19th,2019)the implementation of the third batch of Shanghai drug quantity purchasing ,after the implementation of national “4+7”drug quantity purchasing (Mar. 20th-Oct. 9th,2019). The defined drug frequency (DDDs)and average defined daily cost (DDC) of above 3 periods were calculated according to drug defined daily dose (DDD) recommended by New Pharmacology and related drug instructions ,so as to analyzethe influence of the third batch of Shanghaidrug quantity purchasing and national “4+7”drug quantity purchasing on the use of statins in this hospital and predict the market share trend of each specification in this hospital. RESULTS & CONCLUSIONS :Before the implementation of the third batch of Shanghaidrug quantity purchasing,there were 5 varieties and 8 specifications of statins in this hospital ;after the implementation of quantity purchasing ,it was adjusted to 5 varieties and 9 specifications. The amount of Simvastatin tablets was small in general ,and its consumption sum also continued to decline after the implementation of quantity purchasing. The amount of Rosuvastatin calcium tablets accounted for 49.49% before the implementation of quantity purchasing ,ranking the first ;after the implementation of 3 batches of Shanghai drug quantity purchasing , the amount proportion decreased to Δ 基金项目:上海市科学技术委员会科研计划项目(No.19ZR1450- 600) below 30%,and consumption sum proportion decreased from *本科 。研究方向 :医药市场研究与分析 。电话 :021- 37.82% to 18.77%;after the implementation of national “4+ 54237308。E-mail:2123398711@qq.com 7”drug quantity purchasing ,the consumption sum proportion # 通信作者 :副主任药师 ,博士。研究方向 :临床药学 。电话: continued to decline to 17.38% .The amount of Atorvastatin 021-65690520。E-mail:Hongjun.chen@tongji.edu.cn calcium tablets increased significantly after the implementation 中国药房 2021年第32卷第2期 China Pharmacy 2021Vol. 32 No. 2 ·247· of the thi rd batch of Shanghaidrug quantity purchasing ,from 41.55% to 54.09%,and decreased slightly after the implementation of the national “4+7”drug quantity purchasing ,but the amount proportion was still as high as 53.06%,ranking the first ;before and after the implementation of quantity purchasing ,the proportions of its consumption sum were ranked the first ,which remained at about 50%,being 52.87%,61.18% and 46.50%,respectively. Compared with the amount before the implementation of the third batch of Shanghaidrug quantity purchasing ,the amount of its generic drugs increased by 40.32%,but the consumption sum decreased by 78.18%. Any one type of Pravastatin sodium tablets and Pitavastatin calcium tablets was not selected ;the proportion of them was increased continuously ,but the overall proportion was relatively small. The price of statins decreased significantly after included in quantity purchasinglist. It is expected that the market share of simvastatin in thise hospital will continue to shrink ,and that of atorvastatin may continue to expand. Due to more adverse reactions ,rosuvastatin has limited room to expand ,and pravastatin accounts for a small proportion ,but there is still a demand for patients. Because pitavastatin is a new drug ,its application in this hospital needs more clinical data support.

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