ABSTRACT
AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
ABSTRACT
Abstract Binders are the products that are used to bind, glue or hold the various feed ingredients together in order to maintain pellet integrity. For aqua-culturists, feed manufacturing is an expensive exercise due to the high cost of ingredients along with traditional artificial binders. The use of grain starches as aqua feed binders have advantages which include availability of that binder, nutritional contribution, and minimization of feed cost. A research trial was conducted to test physical properties such as palatability, water stability, dustiness, friability, settling velocity and floatation time of locally available starch i.e. wheat gluten, pea starch and guar gum and to assist their incorporation in on-farm aqua feed. Results revealed that among these three starch, the starch from pea source was proved superior over other two (wheat gluten and guar gum) as all physical quality parameters (dustiness, water stability and friability) revealed better performance of pea starch except pelletability in which guar gum performed best. Although not a single diet proved best in case of flotation time (Tf) and settling velocity (Vset) at varying lengths (6mm, 9mm and 12 mm). This finding indicates the significance of suitable binders for optimal water pollution and sustainable aquaculture. The use of these binders i.e. wheat gluten, pea starch and guar gum in fish feed pellets may also reduce dependence on synthetic binders and minimizes cost.
Resumo Aglutinantes são produtos usados para unir, colar ou manter juntos os vários ingredientes da ração, a fim de conservar a integridade do pellet. Para os aquicultores, a fabricação de ração é uma atividade difícil e cara por causa do alto preço dos aglutinantes artificiais tradicionais. O uso de amidos de grãos como aglutinantes de rações aquáticas tem vantagens que incluem acessibilidade, disponibilidade, contribuição nutricional e minimização do custo da ração. Um ensaio de pesquisa foi conduzido para testar propriedades físicas, como palatabilidade, estabilidade em água, pulverulência, friabilidade, velocidade de sedimentação e tempo de flutuação de amido disponível localmente, ou seja, glúten de trigo, amido de ervilha e goma de guar, e para auxiliar sua incorporação em rações aquáticas. Os resultados revelaram que, entre esses três amidos, o amido de ervilha se mostrou superior aos outros dois (glúten de trigo e goma de guar), pois todos os parâmetros de qualidade física (pulverulência, estabilidade da água e friabilidade) obtiveram melhor desempenho, exceto peletabilidade, em que a goma de guar se destacou. Nenhuma dieta se mostrou melhor no caso de tempo de flotação (Tf) e velocidade de sedimentação em comprimentos variados (6 mm, 9 mm e 12 mm). Essa descoberta indica a importância de aglutinantes adequados para a poluição ótima da água e a aquicultura sustentável. O uso desses aglutinantes, ou seja, glúten de trigo, amido de ervilha e goma de guar, em pellets de ração para peixes também pode reduzir a dependência de aglutinantes sintéticos e minimizar o custo.
ABSTRACT
Binders are the products that are used to bind, glue or hold the various feed ingredients together in order to maintain pellet integrity. For aqua-culturists, feed manufacturing is an expensive exercise due to the high cost of ingredients along with traditional artificial binders. The use of grain starches as aqua feed binders have advantages which include availability of that binder, nutritional contribution, and minimization of feed cost. A research trial was conducted to test physical properties such as palatability, water stability, dustiness, friability, settling velocity and floatation time of locally available starch i.e. wheat gluten, pea starch and guar gum and to assist their incorporation in on-farm aqua feed. Results revealed that among these three starch, the starch from pea source was proved superior over other two (wheat gluten and guar gum) as all physical quality parameters (dustiness, water stability and friability) revealed better performance of pea starch except pelletability in which guar gum performed best. Although not a single diet proved best in case of flotation time (Tf) and settling velocity (Vset) at varying lengths (6mm, 9mm and 12 mm). This finding indicates the significance of suitable binders for optimal water pollution and sustainable aquaculture. The use of these binders i.e. wheat gluten, pea starch and guar gum in fish feed pellets may also reduce dependence on synthetic binders and minimizes cost.
Aglutinantes são produtos usados para unir, colar ou manter juntos os vários ingredientes da ração, a fim de conservar a integridade do pellet. Para os aquicultores, a fabricação de ração é uma atividade difícil e cara por causa do alto preço dos aglutinantes artificiais tradicionais. O uso de amidos de grãos como aglutinantes de rações aquáticas tem vantagens que incluem acessibilidade, disponibilidade, contribuição nutricional e minimização do custo da ração. Um ensaio de pesquisa foi conduzido para testar propriedades físicas, como palatabilidade, estabilidade em água, pulverulência, friabilidade, velocidade de sedimentação e tempo de flutuação de amido disponível localmente, ou seja, glúten de trigo, amido de ervilha e goma de guar, e para auxiliar sua incorporação em rações aquáticas. Os resultados revelaram que, entre esses três amidos, o amido de ervilha se mostrou superior aos outros dois (glúten de trigo e goma de guar), pois todos os parâmetros de qualidade física (pulverulência, estabilidade da água e friabilidade) obtiveram melhor desempenho, exceto peletabilidade, em que a goma de guar se destacou. Nenhuma dieta se mostrou melhor no caso de tempo de flotação (Tf) e velocidade de sedimentação em comprimentos variados (6 mm, 9 mm e 12 mm). Essa descoberta indica a importância de aglutinantes adequados para a poluição ótima da água e a aquicultura sustentável. O uso desses aglutinantes, ou seja, glúten de trigo, amido de ervilha e goma de guar, em pellets de ração para peixes também pode reduzir a dependência de aglutinantes sintéticos e minimizar o custo.
Subject(s)
Starch , Aquaculture , Glutens , Animal Feed/economicsABSTRACT
Las armas de aire comprimido son utilizadas desde hace muchos años con distintos usos que van desde el tiro recreativo hasta el control de plagas. Las más comunes son aquellas que disparan ''balines" o esferas metálicas que pueden llegar a tener capacidad de penetrar tejidos dependiendo del tipo de carga y de la longitud del cañón. Se presenta un caso clínico de un masculino que fue agredido con un arma tipo pistola con carga de CO2 que recibió un impacto a nivel facial y sufrió laceración en piel de labio y fractura dental complicada.
Air guns have been used for many years for a variety of purposes ranging from recreational shooting to pest control. The most common are those that shoot "pellets" or metallic spheres that can penetrate tissues depending on the type of load and the length of the barrel. A clinical case is presented of a male who was assaulted with a CO2-loaded pistol-type weapon, hit at facial level, and suffered laceration of the lip's skin and complicated dental fracture.
Subject(s)
Humans , Male , Middle Aged , Compressed Air , Gun Violence , Tooth Injuries/diagnosis , Costa RicaABSTRACT
ObjectiveTo investigate the effect of Huangqisan pellets （HQS） on the phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and autophagy in the kidney of diabetic nephropathy （DN） rats. MethodDN rat model was established through high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg·kg-1）. DN rats were randomly assigned into model group， irbesartan （0.027 g·kg-1） group， low-dose HQS （0.54 g·kg-1） group and high-dose HQS （1.08 g·kg-1） group. The levels of 24 h urinary total protein （UTP）， serum albumin （Alb）， serum creatinine （SCr）， urea nitrogen （BUN）， triglyceride （TG） and total cholesterol （TC） were measured after 12 weeks of continuous administration. The pathological changes of renal tissue were observed via hematoxylin-eosin （HE） staining. The expression of podocyte split diaphragm proteins nephrin and podocin in the renal tissue were detected by immunohistochemistry. The protein levels and phosphorylation of key proteins in PI3K/Akt/mTOR signaling pathway， as well as the expression of yeast Atg6 homolog （Beclin1） and microtubule-associated protein 1 light chain 3 （LC3） in the renal tissue were analyzed by Western blot. ResultCompared with the control group， the model group showcased increased 24 h UTP， SCr， BUN， TG， and TC levels and decreased Alb level （P<0.01）. After modeling， the rats showed granulosity of epithelial cells of renal tubules， thickening of capillary basement membrane， proliferation of mesangial cells， and sclerosis of glomerulus. Furthermore， modeling down-regulated the expression of nephrin and podocin in the podocyte hiatus of glomerulus （P<0.01） as well as the protein levels of p-PI3K， p-Akt， and p-mTOR and the autophagy markers LC3 and Beclin1 in renal tissue （P<0.01）. Compared with model group， irbesartan and HQS decreased the 24 h UTP， Cr， BUN， TG， and TC levels， increased the Alb level， and alleviated the pathological damage of kidney. Moreover， they up-regulated the expression of Nephrin and Podocin in the podocyte hiatus of glomerulus， as well as the protein levels of p-PI3K， p-Akt， p-mTOR， LC3， and Beclin1 in renal tissue （P<0.05， P<0.01）. ConclusionHQS may inhibit the PI3K/Akt/mTOR signaling pathway to enhance podocyte autophagy and protect the glomerulus， thus slowing down the development of DN.
ABSTRACT
Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
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INTRODUCCIÓN Y OBJETIVO: El rol de la testosterona exógena en la función sexual femenina ha sido estudiado durante muchos años, con resultados contradictorios. En el último tiempo se ha promovido el uso de pellets de testosterona como una solución para mejorar la libido femenina, la cognición, la fuerza muscular y los sistemas cardiovascular y óseo, e incluso evitar el envejecimiento. Por ello, revisamos las publicaciones para tratar de responder si esto es una moda o el tratamiento más innovador del último tiempo. MÉTODO: Se analizaron las bases de datos PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct y ResearchGate. RESULTADOS: De acuerdo con la evidencia, la mejor testosterona disponible es la transdérmica y debe ser usada solo en el trastorno del deseo sexual hipoactivo (TDSH). Los trabajos que evalúan los pellets de testosterona tienen sesgos metodológicos importantes. Si bien son útiles para mejorar la función sexual femenina, producen concentraciones plasmáticas suprafisiológicas de testosterona, por lo que no se puede establecer su seguridad a largo plazo. Tampoco hay datos suficientes que avalen su uso para mejorar el rendimiento cognitivo y el bienestar general, en el tratamiento de enfermedades cardiovasculares o en la prevención de enfermedad ósea. CONCLUSIONES: La testosterona solo se recomienda en el tratamiento del TDSH por vía transdérmica. No recomendamos el uso de pellets de testosterona para el tratamiento de la disfunción sexual ni como hormona antienvejecimiento, ya que no hay estudios consistentes sobre su seguridad, eficacia y efectos adversos a largo plazo.
INTRODUCTION AND OBJECTIVE: The role of exogenous testosterone in female sexual function has been studied for many years with contradictory results. In recent times, the use of testosterone pellets has been promoted as a solution to improve female libido, cognition, muscle strength, cardiovascular system, bone and even prevent aging. Therefore, we will review the publications in order to answer whether this is a fad or the most innovative treatment of recent times. METHOD: The databases PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct and ResearchGate were analyzed. RESULTS: So far, the evidence best testosterone available is transdermal testosterone and that it should be used only in hypoactive sexual desire disorder (HSDD). Papers evaluating testosterone pellets have significant methodological biases. While they are useful in improving female sexual function, they produce supra-physiological plasma levels of testosterone, so their long-term safety cannot be established. There is also insufficient data to support their use in improving cognitive performance and general well-being, treatment of cardiovascular disease or prevention of bone disease. CONCLUSIONS: Testosterone is only recommended for the tratment of HSDD via the transdermal route. We do not recommended the use of testosterone pellets for the treatment of sexual dysfunction or as an anti aging hormone, as there are no consistent studies on its safety, efficacy, and long-term adverse effects.
Subject(s)
Humans , Female , Testosterone/administration & dosage , Sexual Dysfunctions, Psychological/drug therapy , Drug Implants , Androgens/biosynthesisABSTRACT
Resumen En este estudio se analiza y discute la ingesta de plástico y otros materiales antropogénicos por parte de Coragyps atratus en un vertedero de residuos suburbano de Calceta, Provincia de Manabí, Ecuador. De un total de 112 egagrópilas analizadas, el 100% contenía materiales antropogénicos siendo los más conspicuos, diferentes tipos de plásticos y microplásticos, además de metales, vidrio, suelo y otros. Se discute y contrasta con la bibliografía la importancia relativa de los materiales antropogénicos encontrados, así como su potencial impacto en la especie y para el ser humano.
Abstract This study analyzes and discusses the ingestion of plastic and other anthropogenic materials by Coragyps atratus in a suburban waste dump in Calceta, Manabí Province, Ecuador. Of a total of 112 pellets analyzed, 100% contained anthropogenic materials, the most conspicuous being different types of plastics and microplastics, as well as metals, glass, soil, and others. The relative importance of the anthropogenic materials found is discussed and analyzed, same as their potential impact on the species and humanity.
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Se analiza el comportamiento balístico de dos tipos de perdigones "menos letales" usados por las fuerzas policiales en Chile para entender mejor los factores fundamentales que conllevan a la inusual cifra de lesiones oculares en el marco de las manifestaciones masivas ocurridas en Chile desde octubre de 2019. Para evaluar los riesgos de penetración y trauma ocular severo, se construyeron curvas de energía normalizada (E/a) en base a información publicada por las fuerzas policiales y fabricantes de municiones. Aun cuando el riesgo asociado al uso de las municiones según protocolos es leve, este artículo presenta que de todas formas existe riesgo de trauma ocular severo en todas las distancias de uso. La balística de los perdigones, combinada con la imprecisión de municiones multiproyec-tiles, son factores importantes para explicar la alta incidencia de trauma ocular severo. El caso de Chile es parte de un aumento global en la incidencia de lesiones oculares causadas por municiones consideradas menos letales, lo cual demanda una reevaluación de las políticas que regulan su uso.
The ballistic characteristics of two types of "less-lethal" multi-projectile shotgun rounds used by law enforcement in Chile are analyzed to better understand their contribution to the unusually high occurrence of ocular injuries at mass demonstrations since October 2019. Normalized energy (E/a) curves are constructed using publicly-available information from law enforcement and the manufacturers of the munitions to evaluate the risks of skin penetration and severe ocular trauma. Although the risk of penetration is small when these munitions are used according to local protocols, the risk of severe ocular trauma exists at all distances of approved use, and the ballistics of these pelletsalong with the imprecision of multi-projectile shotgun roundshelp to explain the high inci-dence of severe ocular trauma. The example of Chile is part of a worldwide acceleration in the incidence of ocular injuries by "less-lethal" munitions and demands a reevaluation of their suitability for crowd control.
Subject(s)
Chile , Police , Forensic Ballistics , Kinetics , Mass GatheringsABSTRACT
Aim: The present study was carried out to identify and explore novel areas of semiochemical based pest management like oviposition deterrents.Methodology: The oviposition deterrents were identified from larval faecal pellets of pink bollworm using methanol as solvent and analysed in GC-MS. Three fatty acids were identified and evaluated for oviposition deterrent effect. Results: In the present study, three major compounds namely; oleic, linoleic and palmitic acids were identified for the first time from larval faecal pellets of pink bollworm. Their oviposition deterrent effect was confirmed in bioassays carried out with different concentrations of identified compounds. The avoidance index (Ai) 0.78 ± 0.05 and per cent effective deterrency (PED) 87.42% was recorded in oleic acid at highest concentration followed by linoleic acid (Ai: 0.77 ± 0.03; PED: 86.61%) in reducing the egg laying by conspecific female. This clearly showed the role of these compounds as oviposition deterrent. Interpretation: The compounds, oleic and linoleic acids evaluated in laboratory showed oviposition deterrent effect on female pink bollworm reducing egg laying considerably. However, further field studies need to be conducted to validate these observations.
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Introduction: Penetrating ballistic cardiac injury is usuallyfatal before victim the gets any medical help. Retained intracardiac missile is a very rare entity and so far a very few caseshave been reported in the literature.Case report: We describe a young patient who presentedwith multiple life threatening pellet injuries involving chest,abdomen, and limbs. Patient had CT and echocardiographydocumented retained pellets in the heart with pericardialeffusion. Patient was managed successfully using conservativeapproach without any surgical intervention.Conclusion: this case highlights the importance of carefulmonitoring and conservative approach in such critically illpatients for a better outcome.
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OBJECTIVE@#To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS).@*METHODS@#Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software.@*RESULTS@#LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC, AUC, MRT, MRT, t and T of 3, 29-DK after administration in rats ( < 0.05).@*CONCLUSIONS@#Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.
Subject(s)
Animals , Male , Rats , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Rats, Sprague-Dawley , Reproducibility of Results , Tandem Mass Spectrometry , TrichosanthesABSTRACT
@#At present, conventional periodontal treatment cannot achieve complete and effective periodontal tissue regeneration. Cell sheet technology (CST) is a kind of cell transplantation method without scaffold material that can maintain complete extracellular matrix, important ion channels of cells, growth factor receptors, etc., and ensure the interaction between cells and the extracellular matrix. In this paper, the application and research progress of the cell sheet in the field of periodontal tissue regeneration are reviewed. Different types of seed cells can be prepared into monolayer cell sheet, multilayer cell sheet, cell sheet fragments and cell sheet polymers. Among them, the monalayer cell sheet is easily damaged and requires high deoperator; the multilayer cell sheet shows improved mechanical properties, but its thickness needs to be controlled to avoid cell necrosis. The cell sheet fragment can be used in the narrow space between the alveolar bone and root cementum to reduce the difficulty of operation and improve the mechanical properties of the cell sheet. Cell sheet polymers are three-dimensional structures that can provide strong mechanical support and improve the stability of the cell sheet, but the stability of their biological activity needs to be further improved. In methods for construction of the cell sheet, the antifibrosis and antiangiogenesis properties of the amniotic sheet have shown that this structure is suitable as the matrix of cell culture; the method of using a temperature-sensitive culture dish is simple and easy; continuous induction with vitamin C can retain some important proteins on the cell surface; and the magnetic tissue engineering method can increase cell adhesion and easily form a stable cell sheet. The above methods have their own characteristics. In clinical applications, monolayer cell sheet is mainly used for direct transplantation to the receiving site to construct periodontal tissue; multilayer cell sheet of the same or different species overlap and are then transplanted to the receiving site; and multilayer cell sheet of the same kind are wrapped with scaffold material and then transplanted to the receiving site to construct a three-dimensional structure. Overall, cell sheet technology has shown good potential in periodontal tissue regeneration.
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The aim of present work was to investigate blends of Eudragit® NE 30D with Aquacoat® ECD using different ratios to eliminate curing effect associated with individual polymers. Propranolol HCl 10% w/w was layered onto sugar cores using 5% w/w HPMC as a binder. Drug-layered-cores were coated either with pure or blends of Aquacoat® ECD: Eudragit® NE 30D in a fluidized bed coater to obtain 20% w/w coating level. Talc 35% w/w was used as anti-tacking agent. The pellets were characterized for in vitro dissolution studies, morphology, water uptake-weight loss, osmolality and adhesion of coating after curing at 60 °C or 60 °C/75% RH for 24 h. The findings revealed that Aquacoat® ECD coated pellets showed curing effect due to further gradual coalescence of polymeric particles which resulted into better film formation upon curing. In contrast, the curing effect of Eudragit® NE 30D coated pellets was caused by decrease in adhesion of coatings after curing which provided entirely different swelling behavior of uncured (localized swelling) and cured (uniform swelling) pellets. The undesired curing effect of individual polymers was eliminated by using their blends in appropriate ratio.
Subject(s)
Polymers/analysis , /classification , Calorimetry, Differential Scanning/methods , Drug Delivery Systems/adverse effectsABSTRACT
OBJECTIVE： To establish a method for the concentration determination of levofloxacin in rat plasma and compare the pharmacokinetic difference between Levofloxacin tablets and gastric floating sustained-release pellets in rats. METHODS： SD rats were randomly divided into Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group， with 6 rats in each group. They were given relevant medicine intragastrically 40 mg/kg （taking normal saline as solvent）， and the blood samples 0.3 mL were collected before medication and 0.25， 0.5， 1， 2， 4， 8， 12， 24 h after medication. The plasma concentration of levofloxacin in rats was determined by UPLC. The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of 0.1％ formic acid-acetonitrile （78 ∶ 22，V/V） at the flow rate of 0.3 mL/min. The detection wavelength was set at 294 nm， and column temperature was 40 ℃. The sample size was 2 μL. The pharmacokinetic parameters of rats were calculated by using DAS 3.0 software， and the difference between them were detected by F-test. RESULTS： The linear range of levofloxacin was 0.20-20.12 μg/mL， and limit of quantitation was 0.20 μg/mL. The limit of detection was 0.04 μg/mL. The intra-day and inter-day RSDs were less than 10％. The recoveries were all in line with the related requirements of quantitation analysis of the biological samples stated in 2015 edition of Chinese Pharmacopeia. Average drug concentration-time curves of single dose of Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group were all in line with two-compartment model after intragastric administration. The pharmacokinetic parameters cmax were （12.13±1.67） and （8.76±1.13） μg/mL； tmax were（0.86±0.15） and （2.48±0.45）h； t1/2β were（4.67±0.95） and （6.67±1.01）h； AUC0-t were （42.95±4.21） and （126.48±9.44） μg·h/mL； AUC0-∞ were （50.66±6.72） and （132.61±10.63） μg·h/mL， respectively. Compared with Levofloxacin tablets， cmax of Levofloxacin gastric floating sustained-release pellets were decreased significantly， and tmax， t1/2β， AUC and mean retention time were prolonged or increased significantly （P＜0.05）， and relative bioavailability was 294％. CONCLUSIONS： Established UPLC method is simple， specific， sensitive and precise， and can be used for the determination of levofloxacin concentration in rat plasma and its pharmacokinetic study. After levofloxacin is made into gastric floating sustained-release pellets， pharmacokinetic parameters are changed significantly， retention time is prolonged significantly and bioavailability is improved significantly.
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Objective: To optimize andrographolide pellet by using a quality by design (QbD) approach. Methods: Usingthe cumulative in vitro release as evaluation index, the single-factor investigation and hazard analysis were used to study the core and coating process of andrographolide colon-targeting pellets, and the central composite design-response surface method was used to optimize and predict the three key factors of plasticizer dosage, aging time, and coating weight gain. Results: The optimum coating process parameters were as following: plasticizer dosage of 3 g, coating weight gain of 20%, and aging time of 1 h. The process had been verified that the optimal formulation process had a cumulative in vitro release of 6.9% in the acid phase (0.1 mol/L HCl)-buffered salt phase (pH 6.0) and a cumulative in vitro release of more than 90% in the pH 7.2 buffered salt phase. Conclusion: It is feasible to apply the QbD concept optimization in the study of andrographolide colon-targeting pellets.
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Objective: To prepare Gualou-Xiebai intragastric floating pellets(18-24 mesh)by extrusion-spheronization method, and investigate their release characteristics in vitro. Methods: Using the floating time of pellets as indicator and the percentage of microcrystalline cellulose (MCC), octadecanol, hydroxypropyl methylcellulose- K4M (HPMC-K4M)and HPMC-K15M in the solid excipients of the prescription as affecting factors on the basis of single factor experiments, the formulation was optimized by star design-response surface optimization method. Taking the content of 3, 29-dibenzoyl karounitriol in the release medium as the index, the release rate of the pellets in vitro was determined and the release characteristics were explored. Results: The optimum prescription of these pellets was as follows: Gualou-Xiebai dry extract 25 g, MCC 6 g, octadecanol 11 g, HPMC-K4M 3 g, HPMC-K15M 11 g, 70% ethanol solution as wetting agent, and 40% polyvinylpyrrolidone(PVP-K30)solution as binder. The floating time in vitro of the pellets prepared by this prescription was 12 hours, and the cumulative release rate data fitted well with the first-order release model (r>0.97). Conclusion: The Gualou-Xiebai intragastric floating pellets prepared in this study had good floating property and sustained release effect, indicating that the preparation method is feasible.
ABSTRACT
Objective: To prepare Trichosanthes sustained-release pellets and investigate its in vitro release. Methods: Trichosanthes sustained-release pellets were prepared by fluid-bed coating technique.The preparation process of its drug loading layer was optimized by orthogonal experiment with binder, solvent, drug loading and creeping speed of peristaltic pump as the factors of investigation and the yield as the investigation index. The optimum prescription and preparation of the pellets were optimized by single factor test with the content of coating material EC, the amount of poreforming agent PEG4000, the amount of talc powder, the coating weight and the curing time as the factors of investigation and the in vitro release as the investigation index. The in vitro release of the pellets was investigated by high performance liquid chromatography with 3, 29-Diphenyl of Trichosanthes Kirilowii Triol(3, 29-DK)as the detection index. Results: The optimum preparation technology of the drug loading layer was 5% binder, 60% ethanol, 35% drug loading and 0.3 r/min peristaltic velocity of fluid-bed peristaltic pump. The optimum preparation technology of sustained-release layer was 5% EC, 1.5% PEG 4000, 1.25% talc powder, 10% weight gain of coating and 6 h curing. Conclusion: The Tricho- santhes sustained-release pellets prepared in this study were released smoothly. Its production method was simple and easy for operation.
ABSTRACT
OBJECTIVE: To prepare huperzine A micro-porous osmotic pump pellets and to investigate the pharmacokinetic properties in Beagle dogs. METHODS: The extrusion-spheronisation method was used to prepare the core of huperzine A pellets which then coated by fluid-bed coating technology. Central composite design-response surface method was used to optimize the prescription of coating layer.Then Zero-order, First-order and Higuchi equation of cumulative release with time were fitted to study its release characteristics.The commercially available huperzine A tablets were used as reference preparations to investigate the in vivo pharmacokinetics of huperzine A micro-porous osmotic pump pellets, and the bioequivalence of the two preparations were compared. RESULTS: The formula of coating was optimized as followsEC of 61.5%, PEG400 of 10.5%. Zero-order kinetics existed in the release of the pellets in 24 h. Moreover, the osmotic pressure-controlled delivery was greatly responsible for drug release. In vivo study showed that tmax and ρmax of huperzine A micro-porous osmotic pump pellets were significantly lower than that of the reference preparation, and its t1/2 was significantly prolonged compared with the reference preparation, the relative bioavailability was 95.8%. CONCLUSION: Huperzine A micro-porous osmotic pump pellets had a better sustained release effect in the Beagle dog and have a good correlation in vivo.
ABSTRACT
Extrusion-spheronisation method was used to prepare Rhus chinensis total phenolic acid pellets. The formula and preparation of R. chinensis total phenolic acid pellets were optimized. The formulas( drug loading capacity,diluent,wetting agent and anti-sticking agent) were determined by the single factor test with yield,appearance and performance as the indexes. The preparation was optimized by Box-Behnken design and response surface method,with the rate of extrusion,rate of spheronization and time of spheronization as the independent variables and the overall desirability value of yield,friability and roundness as the dependent variables. The optimal formula of pellets was as follows: drug loading capacity 28. 7%,MCC-lactose 9 ∶1,silicon dioxide as anti-sticking agent,and 60% ethanol as wetting agent. The optimal preparation was determined as follows: the rate of extrusion was 43 r·min-1,the rate of spheronization was 1 800 r·min-1,and the time of spheronization was 4 min. The absolute deviation between predicted value and estimated value under the conditions was less than 5. 0%,with a high degree of model fit. The preparation parameters obtained were accurate,reliable and reproducible. Under scanning electron microscopy( SEM),R. chinensis total phenolic acid pellets were uniform in diameter,round and smooth. The optimal formulation and process are stable and feasible for preparing R. chinensis total phenolic acid pellets.