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ObjectiveTo investigate the analgesic effect and mechanism of Osteoking （OK） on nerve compression in lumbar disc herniation. MethodThe rat model of chronic compression of dorsal root ganglion （CCD） was established to simulate clinical lumbar disc herniation. The CCD rats were randomly divided into model group， low， medium， and high dose OK groups （1.31， 2.63， 5.25 mL·kg-1·d-1）， and pregabalin group （5 mg·kg-1）， with eight rats in each group. Another eight SD rats were taken as the blank group， and the same volume of normal saline was given by gavage. Behavioral tests， side effect evaluation， network analysis， Western blot， immunofluorescence， and antagonist application were used to explore the effect. ResultCompared with the blank group， the mechanical hyperalgesia threshold， thermal hyperalgesia threshold， and the expression of inflammatory factors in the spinal dorsal horn of the model group are significantly increased （P<0.01）， and the related indicators of the affected foot footprints are significantly down-regulated （P<0.01）. The expression of signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， and phosphorylated extracellular regulated protein kinase （p-ERK） in microglia in the spinal dorsal horn is significantly increased in the model group （P<0.01）. Compared with the model group， low， medium， and high dose OK groups can increase the mechanical hyperalgesia and thermal hyperalgesia thresholds of CCD rats （P<0.05， P<0.01） in a dose-dependent manner， improve the gait of CCD rats （P<0.05， P<0.01）， and reduce the expression of inflammatory factors in the spinal dorsal horn （P<0.05， P<0.01）. The expression of STAT3， VEGFA， and p-ERK in the spinal dorsal horn microglia of CCD rats is significantly decreased （P<0.05， P<0.01）， and the acetic acid-induced nociceptive response in rats is effectively reduced （P<0.05， P<0.01）. In addition， there is no tolerance. The results of the body mass test， organ index， forced swimming， and rotation show that OK has no obvious toxic or side effects. Further antagonist experiments show that MRS1523 and RS127445 can reverse the transient analgesic effect of OK compared with the high dose OK group （P<0.01）. ConclusionOK has a good analgesic effect on the CCD model without obvious toxic side effects， and its mechanism may be related to the activation of ADORA3 and HTR2B and the inhibition of STAT3， VEGFA， p-ERK， and other elements in microglia.
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The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
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Polisorbatos/química , Flavonoides , Pueraria , Tensoactivos/química , Etanol , Emulsiones , Tamaño de la Partícula , SolubilidadRESUMEN
Proteases are ubiquitously present and are among the largest groups of commercially important enzymes. Here, we investigated a wood-rot basidiomycete Trametes versicolor (L.) Lloyd [Syn. Coriolus versicolor (L.) Quél.; Polyporus versicolor (L.) Fr.] as a source of the enzyme serine protease, its production, and optimized to obtain a higher yield of the enzyme.. The significant variables with optimized values for maximum production of the enzyme were temperature (30?C), incubation time (120 h) and wheat bran (10 g). The yield increased by 30.76% by statistically optimizing the media. The optimized temperature and pH for the maximum protease activity was 50?C and pH 7.0, respectively. The enzyme was purified through ion exchange (using DEAE cellulose 52 resin) and gel filtration chromatography (using Superdex 200 column). The purified enzyme had a retention time of 7 min in RP-HPLC. The enzyme was stable at a broad range of temperature (30-60?C) and pH (5.0-8.0) with a half-life of 58.72 min, Vmax of 37.17 ?M min/mL and Km of 0.657 mg/mL. Its activity was enhanced by Na+, Ca2+, Mg2+ ions and SDS surfactant. These properties make this enzyme a valuable candidate for industrial applications
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Citalopram is an antidepressant used for treating major depressive disorder. In the current work Citalopram HBr is formulated as mouth dissolving film with enhanced drug dissolution. The Central Composite Design (CCD), employed to examine the effects of amount of HPMC E50 (A), amount of maltodextrin (B) and amount of glycerol (C) on response variables tensile strength, disintegration time and cumulative % drug release. 27 formulations prepared according to CCD and evaluated for physicochemical parameters and in vitro dissolution studies. Citalopram HBr mouth dissolving films formulated by employing solvent-casting method using HPMC E50, maltodextrin and glycerol, optimized for the effective dosage of superdisintegrants. The formulation CF21 with maximum tensile strength of 67.21±1.31 gm, least disintegration time of 9±1.60 sec and highest drug release of 98.41±1.81% is chosen optimal formulation with maximum content uniformity and folding endurance. It is evident from the above results that the developed formulation can be an innovative dosage form to improve the drug delivery, quick onset of action as well as improve patient compliance in the effective management of depression.
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@#Introduction: Moringa oleifera Lam. is a miracle tree that has been widely utilised in folklore medicine due to its immense amount of phenolic constituents that could treat various ailments. Different techniques have been implemented to extract the phenolic but the parameters may not be optimised to further enhance the amount of phenolic extracted. Thus, the work aimed to enhance phenolic content and antioxidant activity of M. oleifera through RSM methodology, which is rapid and convenience. Methods: At first, antioxidant activity of different parts of M. oleifera (leaves, stem, pod and seed) were investigated. The plant part with the highest antioxidant activity was selected for the optimisation of extraction condition using RSM. In RSM, temperature (XA), extraction time (XB) and solid-liquid ratio (XC) were employed to study the effects on yield, total phenolics, flavonoids and antioxidant activity. Then, the optimum extraction condition obtained via RSM was utilised in LC-MS and HPLC analysis to determine the potential bioactive constituents. Results: The leaves of M. oleifera displayed the highest antioxidant activity as compared to other plant parts. The optimum extraction condition obtained for the leaves extract was: temperature (XA): 82°C, extraction time (XB): 48 min and solid-liquid ratio (XC): 1:30 g/mL (w/v). Meanwhile, LC-MS revealed the presence of gallic acid, chlorogenic acid, quercetin, kaempferol and 3-O-glucoside kaempferol. HPLC analysis detected six compounds; gallic acid, epicatechin gallate, chlorogenic acid, myricetin, quercetin and kaempferol. Conclusion: The optimisation are promising to improve yield and antioxidant activity in M. oleifera as compared to non-conventional extractions.
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OBJECTIVE: To optimize the formulation of econazole solid lipid nanoparticles(E-SLN) by combining pseudo-ternary phase diagrams and central composite design-response surface methodology (CCD-RSM). METHODS: Econazole solubility in different solid lipids and the capacity of lipid emulsion were tested. The microemulsion region was obtained by the pseudo-ternary phase diagrams. Then the E-SLN were prepared by microemulsion method. Drug/lipid (X1), lipid/surfactant (X2) and surfactant/cosurfactant (X3) were taken as individual factors, the encapsulation efficiency (Y1), particle size (Y2), Zeta potential (Y3) were taken as the dependent factors. The possible optimum formulation was predicted by CCD-RSM and validated. RESULTS: Econazole could be dissolved in tripalmitic acid glyceride (TAG), monostearic acid glyceride, stearic acid and lauric acid glyceride. TAG had a good capacity of emulsion. The optimized formulation was econazole 0.06 g, glyceryl palmitate 0.48 g, Tween-80 1.194 g, glycerol 0.274 g and added water to 30 mL by CCD-RSM. According to the optimized formulation, the encapsulation efficiency, particle size and Zeta potential were (94.06±1.54)%, (18.88±0.38)nm and (3.53±0.01)mV, respectively. The deviation was less than 5%. CONCLUSION: The stable and ultra-small size E-SLN with high encapsulation efficiency could be obtained by combining pseudo-ternary phase diagrams and CCD-RSM.
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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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According to Quality by Design (QbD) concept, quality should be built into product/method during pharmaceutical/analytical development. Usually, there are many input factors that may affect quality of product and methods. Recently, Design of Experiments (DoE) have been widely used to understand the effects of multidimensional and interactions of input factors on the output responses of pharmaceutical products and analytical methods. This paper provides theoretical and practical considerations for implementation of Design of Experiments (DoE) in pharmaceutical and/or analytical Quality by Design (QbD). This review illustrates the principles and applications of the most common screening designs, such as two-level full factorial, fractionate factorial, and Plackett-Burman designs; and optimization designs, such as three-level full factorial, central composite designs (CCD), and Box-Behnken designs. In addition, the main aspects related to multiple regression model adjustment were discussed, including the analysis of variance (ANOVA), regression significance, residuals analysis, determination coefficients (R2, R2-adj, and R2-pred), and lack-of-fit of regression model. Therefore, DoE was presented in detail since it is the main component of pharmaceutical and analytical QbD.
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Proyectos de Investigación/tendencias , Preparaciones Farmacéuticas/análisis , Preparaciones Farmacéuticas/normas , Gestión de la Calidad TotalRESUMEN
Objective To optimize prescription and evaluate the quality of imperatorin lipid microspheres (ILM) by central composite design-response surface methodology (CCD-RSM), therefore to use the mean particle size, particle size distribution (polydispersity index, PDI) and Zeta potential as the primary indicator. Methods Mean particle size, particle size distribution and Zeta potential of lipid microspheres were measured to investigate the effect of the concentration of egg yolk lecithin, poloxamer and percentage of soybean oil in oil phase on the properties of ILM preparation. Mathematic relation between indicator and factor was constructed by binominal fitting. Then the response surface method according to the best mathematical model of evaluation indicators was used to make predictive analysis of the best prescription. Optimized prescription was used to prepare ILM and evaluate its quality. Results Optimized prescription was egg yolk lecithin 1.50 g, F68 0.35 g, and MCT 10 g. All items of optimized prescription were similar to target values. According to the optimized prescription, mean particle size of ILM was (165.00 ± 0.22) nm, particle size distribution was 0.046 ± 0.070, Zeta potential was (−30.30 ± 0.13) mV, encapsulation efficiency was about 90.09%, drug-loading rate was 1.0 mg/mL. Conclusion Due to the better predictability of constructed mathematical model, CCD-RSM can be applied to optimize prescription of lipid microspheres and the optimized ILM meet pharmacy requirements.
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Objective: To optimize the purification technology of saponins in steamed Panax notoginseng with macroporous resin. Methods: The main factors affecting the purification process were screened by failure mode and effects analysis (FMEA). The purification method with macroporous resin was optimized by central combination design-response surface method (CCD-RSM) based on the recovery and purity of saponins. In this experiment, the concentration of sample solution, loading volume, washing volume, ethanol concentration, and ethanol elution volume were used to investigate the purification of saponins in steamed P. notoginseng. Results: The optimized purification process with macroporous resin was as follows: maximum recovery (82.81%) and purity (77.24%) of saponins were obtained with the concentration of saponin solution of 11.22 mg/mL, loading volume of 4.97 BV, washing volume of 2 BV, ethanol concentration of 70%, and ethanol elution volume of 3.31 BV. Conclusion: The optimized purification process based on FMEA and CCD-RSM is convenient and stable, with high recovery and purity of saponins, which has a certain practical value.
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Digital radiography has evolved and co-existed with the dental imaging since four decades. The complete replacement of digital imaging in place of conventional screen-film combination has proved to be beneficial to the new era of dentistry. Because of low cost, higher patient comfort, increased dose efficiency, and greater dynamic range of digital detectors with possible reduction of radiation exposure to the patient, the digital imaging has created a new place for itself not only in medical radiology but in dentistry as well. The future will be digital, irrespective of CCDs, CMOS, or phosphor plates the advancement in the field of imaging is rapid and progressive with constantly replacing the older ones. The present paper discusses thoroughly about the various advancements in digital imaging starting from CCDs to flexible phosphor plates. Digital imaging, a substitute for conventional film radiography, has ventured into the arena of dentistry as well and revolutionised the imaging concepts of Oral Health Care Professionals.
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Objective To make portable the detector for up-converting phosphor (UCP) immune lateral flow assay portable and increase the test precision by developing an area CCD-based detection system for UCP immune lateral flow assay.Methods The excitation light source was a 980 nm and 300 mW laser diode.In order to decrease the error induced by the un-uniformity of laser irradiation,a uniformity mirror was inserted in the beam and a calibration algorithm was optimized.The residual error from the un-uniformity irradiation was less than 1％.Results Thanks to the adjustability of the exposure time,the dynamic range of detection of the system was as high as 106 dB.The repeat test error for the very low signal was 1％ (variation coefficient).The linear correlation coefficient between the tested T/C value and sample concentration was 0.998.Conclusion Compared to is traditional instrument,this detection system is static,portable and highly precise.
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Objective To compare the exposure to heart and other organs of the application of DIBH (deep inspiration breath-hold)and FB(free breath)in the left breast cancer radiotherapy,and the relationship between CCD(cardiac contact distance)and heart dose was analyzed.Methods Thirty patients with left breast cancer were examined with CT scans using DIBH and FB respectively,and then the dose was calculated by TPS(treatment planning system).The dose of heart,left anterior descending branch and left ventricle were analyzed by DVH(dose volume histogram).FB-CCDax(Axial cardiac chest wall contact distance)and FB-CCDps(sagittal heart chest wall contact distance)in CT images were measured based on FB.Results The parameters showed that,in radiotherapy with the application of DBIH technology,the irradiated volume of heart, left anterior descending branch(LAD),left ventricle(LV)of were significantly lower than that in the organs in the FB,the mean dose(Dmean)of heart of the former was 0.8 Gy,compared with 2.7 Gy in the latter one(P<0.005).The Dmean of LAD was 4.0Gy,compared with 12.7Gy in the latter one(P<0.001); The Dmean of LV was 1.2Gy,compared with 3.6Gy in the latter one(P<0.005).In the DIBH and FB radiotherapy,the Dmean of the heart,left anterior descending branch and left ventricle was correlated with FB-CCDps,but not with FB-CCDax.Conclusion DIBH is a simple treatment technique that can effectively reduce the cardiac radiation dose without loss of target dose.FB-CCDps is a potential predictor of cardiac exposure,and the longer the FB-CCDps distance is,the higher the cardiac dose is.The study found that at least 70% of patients with left breast cancer would benefit from DIBH and reduce the radiation exposure to normal cardiac structures,so DIBH should be used as a routine clinical application.
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Objective: To optimize the processing technology of Hemsleya omeiensis processed by licorice juice. Methods: HPLC was employed to determine the content of hemslecin A.Taking content of hemslecin A as index, the orthogonal test was adopted to optimize the covered moistening time, drying-time, and processing temperature. And the central composite design-response surface methodology (CCD-RSM) was adapted to optimize moistening time and drying-time further. Results: The optimum processing technology of H. omeiensis by the orthogonal test was covered moistening time of 7 h, drying-time of 12 h, and processing temperature at 80℃. The optimum processing technology by CCD-RSM was covered moistening time of 7.48-8.56 h, drying-time of 12.06-13.12 h, and processing temperature at 80℃. Conclusion: The experimental design method is precise and the data are reliable with the model. It is the first time that H. omeiensis is processed with licorice juice. Besides, it establishes the processing technology of H. omeiensis and provides a theoretical basis for the processing technology of H. omeiensis with licorice juice.
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The purpose of this paper was to study the pre-mixed materials of emulsion gel. Accessories were screened and formula was designed with the most common use, low cost and simple process as the standards. Experiments were designed by central composite design-response surface methodology (ccd-rsm). 8.0.6 Trial Design-Expert was used for data processing and analysis, and subjective scores were used as the index to draw the three-dimensional effect surface and 2D contour maps. It was determined that the optimal ranges were A (carbomer 940)： 0.05-0.065 g; B (castor oil)： 1.00-1.12 mL; C (poly polysorbate-80)： 0.15 mL. The optimal formula was as follows： carbopol 0.057 5 g, castor oil 1.1 mL, polysorbate-80 0.15 mL. The formulated substrate was studied on its preliminary stability and rheology characteristics, such as viscosity and thixotropy. Then with the optimal formula as substrate, emulsion type gel was prepared respectively with 98% rutin, 98% berberine hydrochloride, and 98% berbamine hydrochloride as the main component. With 0.9% normal saline as the absorption solution, the results showed that the ransdermal flux of the three formulations of 1 h was all less than 1%. The results indicated that this substrate had the potential to be developed into a premixed material. The emulsion type gel matrix made from this formula had a good appearance, stability to certain extent, appropriate viscosity and thixotropy, and showed no skin irritation in 1 h.
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Se caracterizaron los extractos etanólicos de hojas y cortezas de 13 especies de la familia Lauraceae mediante cromatografía en capa fina de dos dimensiones (2D-CCD). Los datos posteriores se analizaron mediante técnicas de análisis estadístico multivariado (cluster y análisis de componentes principales (PCA)). Lo anterior permitió hacer una distinción entre los extractos obtenidos de diferentes partes de la planta (hojas y cortezas). Se observó, además, que la metodología usada es capaz de diferenciar entre extractos obtenidos a partir de especies de Lauraceae y los de otras familias de plantas.
Leaves and barks ethanolic extracts from 13 Lauraceae species were characterized through two-dimensional thin layer chromatography (2D-TLC). The subsequent data was analized through multivariate statistical analysis techniques (cluster analysis and principal components analysis (PCA)). This allowed to do a distinction between extracts obtained from different parts of the plant (leaves and bark). In addition, it was observed that the implemented methodology is able to differentiate between extracts obtained from Lauraceae species and some obtained from other plant families.
Caracterizaram-se os extratos etanólicos de folhas e casca obtidos a partir de espécies da família Lauraceae por cromatografia em camada fina em duas dimensões (2D-CCF). Os dados obtidos foram analisados utilizando técnicas de análise estatística multivariada tipo análise de cluster e análise de componentes principais (PCA). As técnicas estadísticas permitiram fazer uma distinção entre os extratos obtidos a partir de diferentes partes da planta (folhas e casca). Além disso, observou-se que o método utilização é capaz de diferenciar entre os extratos provenientes de espécies de Lauraceae daqueles obtidos a partir de outras famílias de plantas.
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OBJECTIVE: To prepare the inclusion complex of Lignum dalbergia odorifera oil with hydroxyl-β-cyclodextrin (HP-β-CD), and to optimize the preparation process of it. METHODS: The inclusion complex was prepared by the stirring-freeze-dry meth od. The preparation process was optimized by central composite design-response surface method (CCD-RSM), with the colligation score which was calculated by the yield of inclusion, the utilization rate of volatile oil and the content of trans-nerolidol as index. The inclu sion complex was verified by phase-solubility method, DSC,UV and microscopical identification. RESULTS: The optimum inclusion technology was: inclusion solvent 5% ethanol, stirring rate 500 r·min-1, HP-β-CD to volatile oil 33:1, inclusion temperature 42℃, inclusion time 2.5 h. The formation of inclusion complex can change the solubility, optical and thermodynamic properties of volatile oil. CONCLUSION: The preparation process of inclusion complex of Lignum dalbergia odorifera oil with HP-β-CD optimized by CCD-RSM is reasonable and feasible, and provide a reliable experiment basis for its application.
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Union Total is herbal formulation made in the form of capsule which contains two standardized plant extracts Cissus quadrangularis (CQ) and Withania somnifera (WS). The present work describes development and validation of High Performance Thin Layer Chromatographic method for simultaneous analysis of Stigmasterol (STG) in Cissus quadrangularis (CQ) and Withaferin A (WFA) in Withania somnifera (WS). Stigmasterol and Withaferin A were identified on silica G60 F254 HPTLC plates by post derivatization technique and robustness study was performed by applying a central composite design (CCD) with k factor having 2k factorial runs, 2k axial experiments and five center points. In HPTLC good separation was obtained with chloroform: methanol: toluene: formic acid (6.5: 0.5: 3: 0.25 v/v/v/v) as mobile phase and anisaldehyde sulphuric acid as a derivatizing reagent at detection wavelength 530 nm. Linearity was obtained in the concentration range of 100-200 ng/band for WFA and 200-700 ng/band for STG and the % recoveries were found in the range of 100.06 % to 100.46 % for WFA and 99.97 % to 100.94 % for STG respectively. HPTLC method was found to be sensitive, precise, accurate and reproducible, which would be of use in quality control of these tablets.
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Objective The biological half-life in vivo of local anesthesia is short, high concentration in local tissue is in-clined to cause central nerve and cardiovascular toxicity due to the drug absorption into blood by blood vessels.The research was to pre-pare the poly ( lactide-co-glycolide) nanoparticle loaded with ropivacaine ( RVC-PLGA-NPS) , optimize its process, and determine its characteristics in vitro. Methods An oil-in-water emulsion solvent evaporation technique was adopted to prepare the RVC-PLGA-NPS.The formulation was optimized by central composite design/response surface method(CCD-RSM), with the encapsulation effi-ciency( EE) , drug loading( DL) and particle size as the indexes.Research was also made on itsin vitro release by fitting different model equations. Results The acquired nanoparticals were smooth, with the mean particle size (331.21±2.11) nm, DL (13.81±1.35)%and EE (74.82±2.53)%.The accumulative release rate of the nanoparticals was about 73%in 96 h, which showed that Higuchi func-tion fitted the release curve. Conclusion The RVC-PLGA-NPS made by emulsion solvent evaporation technique have obvious drug-release behaviour in vitro.
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Objective:To investigate the craniofacial features in patients with cleidocranial dysplasia (CCD).Methods:The facial features,cervical vertebral bone age and skeletal abnormalities of 8 patients with CCD were studied by analyzing facial photos,cephalo-metric and panoramic radiographs.Results:4 patients were in the early growth stage and the other 4 in the late period of development. The bossing forehead and inclined eye fissure were observed in all patients,but underdevelopment of midfaces were not obviously pres-ented in younger patients.Morphological abnormalities of craniofacial bones,such as ascending ramus,coronoid process,nasal bones and disappearence of gonial angle were observed in all patients.Conclusion:Some craniofacial malformations in patients with CCD may be presented earlier than underdeveloped midface,which can be helpful for early diagnosis of CCD.