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1.
Choline fenofibrate is the choline salt of fenofibric acid, which releases free fenofibric acid in the gastrointestinal tract. To estimate the absolute oral bioavailability of fenofibric acid and choline fenofibrate, a novel and sensitive UPLC–MS/MS method with liquid–liquid extraction procedure was developed for the determination of fenofibric acid in rat plasma. The separation was achieved on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 μm) containing 2 mm ammonium acetate–methanol with a gradient elution program. Validations of this method including specificity, sensitivity (limit of quantification, 5 ng/mL), linearity (0.005–10 μg/mL), accuracy (within ±4.3%), precision (intra‐ and inter‐day coefficient of variation <11.3%), recovery (94.9–105.2% for fenofibric acid), matrix effect, stability and dilution, were all within acceptable limits. This method successfully supported the determination of fenofibric acid and choline fenofibrate. The absolute oral bioavailability was 93.4% for choline fenofibrate and 40.0% for fenofibric acid. These results suggested that choline fenofibrate and fenofibric acid had a better in vivo pharmacokinetic behavior than that of fenofibrate. The two new orally administrated pharmaceuticals, fenofibric acid and choline fenofibrate, can be developed as alternatives to fenofibrate.  相似文献   

2.
In this study, the rapid expansion of supercritical solution (RESS) process was used to precipitate fine solid particles of amoxiccilin where supercritical carbon dioxide was used as a solvent. The process has been done by changing the RESS parameters, including extraction pressure (150–210 bar), extraction temperature (313–333 K), nozzle length (2–15 mm), effective nozzle diameter (450–1700 µm), and spraying distance (1–10 cm), to investigate the effect of these parameters on the size and morphology of the precipitated amoxicillin particles. The characterization (size and morphology) of the particles was examined using scanning electron microscopy (SEM). Based on the different experimental conditions, the mean particle size of the fabricated particles were between 1.08 and 5.72 µm, while the intact particles of amoxicillin were about 41.46 µm. Also, no regular changes in the morphology of the processed particles were observed.  相似文献   

3.
Column chromatography of the stem aqueous methanolic extract of Dracaena reflexa Lam. (DRSE) led to the isolation of five flavonoids, one phenolic glycoside, one triterpenoid and two steroidal saponins. Furthermore, 44 compounds were tentatively identified in the phytoconstituent profile of DRSE using HPLC–ESI–MS/MS. The antioxidant activity of DRSE was evaluated. In a DPPH radical scavenging assay, DRSE exhibited an IC50 value of 311.6 ± 10.10 μg/ml compared with the IC50 value of the standard Trolox (24.42 ± 0.87 μg/ml). The antioxidant activities of DRSE using ABTS assay and ferric reducing antioxidant power assay were 326.63 μm Trolox equivalents/mg extract and 208.67 μm Trolox equivalents/mg extract, respectively. The wound-healing activity of DRSE was studied by the scratch assay using Human Skin Fibroblast cells. After 24 h DRSE (at 10 and 20 μg/ml) decreased the wound width to 0.55 ± 0.37 and 0.47 ± 0.55 mm, respectively, compared with the wound width in the control cells (0.77 ± 0.17 mm). This result suggested that DRSE improved the wound-healing process by inducing the migration of fibroblasts. Moreover, a docking study was performed to evaluate the binding affinity of the identified phytoconstituents toward GSK-3β relative to the co-crystalized inhibitor and curcumin with the possible involvement of this pathway in the wound-healing activity of the extract.  相似文献   

4.
Excessive reactive oxygen species (ROS) can oxidatively damage DNA to cause severe biological consequences. In the study, a natural flavonoid, myricitrin (myricetin‐3‐O‐α‐L‐rhamnopyranoside), was found to have a protective effect against hydroxyl‐induced DNA damage (IC50 159.86 ± 54.24 μg/mL). To investigate the mechanism, it was determined by various antioxidant assays. The results revealed that myricitrin could effectively scavenge ·OH, ·O2?, DPPH· (1,1‐diphenyl‐2‐picrylhydrazyl radical), and ABTS+· (2,2′‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals (IC50 values were respectively 69.71 ± 5.93, 69.71 ± 5.93, 25.34 ± 2.14, and 1.71 ± 0.09 μg/mL), and bind Cu2+ (IC50 27.33 ± 2.36 μg/mL). Based on the mechanistic analysis, it can be concluded that: (i) myricitrin can effectively protect against hydroxyl‐induced DNA oxidative damage via ROS scavenging and deoxynucleotide radicals repairing approaches. Both approaches can be attributed to its antioxidant. From a structure‐activity relationship viewpoint, its antioxidant ability can be attributed to the ortho‐dihydroxyl moiety, and ultimately to the stability of its oxidized form ortho‐benzoquinone; (ii) its ROS scavenging is mediated via metal‐chelating, and direct radical‐scavenging which is through donating hydrogen (H·) and electron (e); and (iii) its protective effect against DNA oxidative damage may be primarily responsible for the pharmacological effects, and offers promise as a new therapeutic reagent for diseases from DNA oxidative damage.  相似文献   

5.
超临界流体沉淀技术制备超细粒子研究   总被引:3,自引:0,他引:3  
超临界流体沉淀(简称SFP)技术以其特有的优点成为引人注目的在无机化学、有机化学、医药等领域具有广阔应用前景的超细微粒制备方法.为充分发挥SFP技术的优势,科研工作者以RESS与SAS为基础提出了ASES、SEDS、SAS-EM等各种新技术.本文着重综述了以RESS及SAS为基础发展起来的SFP新技术的原理、特点及相关的应用,指出了目前SFP技术存在的问题及今后的研究方向.  相似文献   

6.
The films of N‐ethyl chitosan were prepared via the solution‐casting technique with formic acid as a solvent. The solutions with different concentrations (35 and 40 wt %) were prepared previously from dilute solution (1 wt %) via evaporating process. The crystalline morphology of these films was investigated by means of polarized optical microscopy and scanning electron microscopy. Normal spherulites with a low growth rate formed in the casting films. The different morphologies of spherulite appeared in the films cast from the solutions with different concentrations. After further crystallizing for a few days, the spherulites were decorated by thousands of needlelike extended‐chain crystals, which had a typical size of ~50 μm (length) × 2~5 μm (width) × 1~2 μm (height) in the central part of the spherulite, but a typical size of ~5 μm (lenght)× 1~2 μm (width) × 1~2 μm (height) in the fringe part of the spherulite. The real concentration for crystallization was determined to be 65–82 wt%. Thus, the crystallization actually appeared in supersaturated solution. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 2033–2038, 2003  相似文献   

7.
Cordycepin has recently received increased attention owing to its extensive pharmacological activity. Adenosine deaminase (ADA) is widely distributed in mammalian blood and tissues; as a result, cordycepin is quickly metabolized upon entering into the body and converted into the inactive metabolite 3′-deoxyinosine, thus limiting its activity when administered alone. We herein present a novel ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method for screening ADA inhibitors against the metabolism of cordycepin. Cordycepin and 3′-deoxyinosine were chosen as substrate and product, respectively. A proper separation was achieved for all analytes within 3 min. 3′-Deoxyinosine was quantified in the presence or absence of potential ADA inhibitors to evaluate ADA activity. The assay can simultaneously determine substrate and product, with the endogenous substance and ADA inhibitors added not interfering in its activity. After optimizing the enzymatic incubation and UHPLC–MS/MS conditions, Km and Vmax values for ADA deamination of cordycepin were 95.18 ± 7.85 μm and 363.90 ± 12.16 μmol/min/unit, respectively. Oleanolic acid and ursolic acid from Ligustri Lucidi Fructus were chosen as ADA inhibitors with half maximal inhibitory concentration values of 21.82 ± 0.39 and 18.41 ± 0.14 μm , respectively. A non-competitive inhibition model was constructed and this assay can be used to screen other potential ADA inhibitors quickly and accurately.  相似文献   

8.
This work reports a novel fabrication technique for development of channels on paper‐based microfluidic devices using the syringe module of a 3D printing syringe–based system. In this study, printing using polycaprolactone (PCL)‐based ink (Mw 70 000‐90 000) was employed for the generation of functional hydrophobic barriers on Whatman qualitative filter paper grade 1 (approximate thickness of 180 μm and pore diameter of 11 μm), which would effectively channelize fluid flow to multiple assay zones dedicated for different analyte detection on a microfluidic paper‐based analytical device (μPAD). The standardization studies reveal that a functional hydrophilic channel for sample conduction fabricated using the reported technique can be as narrow as 460.7 ± 20 μm and a functional hydrophobic barrier can be of any width with a lower limit of about 982.2 ± 142.75 μm when a minimum number of two layers of the ink is extruded onto paper. A comparison with the hydrodynamic model established for writing with ink is used to explain the width of the line printed by this system. A fluid flow analysis through a single channel system was also carried out to establish its conformity with the Washburn model, which governs the fluid flow in two‐dimensional μPAD. The presented fabrication technique proves to be a robust strategy that effectively taps the advantages of this 3D printing technique in the production of μPADs with enhanced speed and reproducibility.  相似文献   

9.
A simple and robust HPLC method with electrochemical detection was developed for the quantitative determination of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a DNA damage product excreted in urine. Sample cleanup was carried out using solid-phase extraction (SPE) prior to chromatographic separation. 8-OHdG was well separated on an Eclipse XDB®-C18 column (150 × 4.6 mm i.d., 5 μm) with an Eclipse XDB®-C18 guard column (12 × 4.6 mm i.d., 5 μm). Two mobile phases containing methanol and 10 mM sodium formate (pH 4.5) at a ratio of 10: 90 and 50: 50 v/v, respectively, were used. The retention time of 8-OHdG was 9.8 ± 0.5 min. The recovery of 8-OHdG was found to be 97.2 ± 3.3% (n = 6). Intraday and interday precisions of the method were 4.0 ± 2.9% (n = 6) and 6.6 ± 1.7% (n = 6), respectively. The detection limit was 5 ng/mL. Preliminary investigation showed that the mean value of 8-OHdG, normalized with the amount of creatinine in the sample, from the thalassemic group was significantly higher than that from healthy subjects (211 ± 214 ng/mg creatinine vs. 31.4 ± 32.2 ng/mg creatinine, respectively), indicating oxidative stress.  相似文献   

10.
The length of cellulose nanofibrils (CNFs) is a significant parameter for various applications. The goal of this research was to employ a fabrication method to produce length-controlled CNFs; the chosen technique was enzy-grinding (enzyme pretreatment followed by mechanical grinding). Here, we presented the results of the optimization of the diameter and length, the characterization of the properties of CNFs and nanofilms prepared using these fibrils. The cellulose morphology, crystallinity index (CrI), chemical structure, and thermal stability were investigated as functions of the enzyme loading and hydrolysis time. The results showed that enzy-grinding could effectively reduce the diameter and length of cellulose fibrils. The average diameter was about 8.6 ± 3.6 nm, and the length could be controlled over the range from 0.76 ± 0.38 μm to ≥ 4 μm (i.e. aspect ratios from 43 to ≥ 328). After the grinding process, the CNFs maintained high thermal stability and no change in the chemical structure compared to the original pulp. The transmittance and mechanical properties of the CNF films were strongly dependent on the fibril length. The fabrication of length-controlled CNFs using the enzy-grinding process is meaningful and significant research which could be relevant to the optimization of such materials for various applications.  相似文献   

11.
Caesalpinia sappan L . is a traditional medicinal plant which is used for promoting blood circulation and cerebral apoplexy therapy in China. Previous reports showed that the extracts of Caesalpinia sappan L . could exert vasorelaxant activity and anti‐inflammation activity. Protosappanin B is a major constituent of C. sappan L. , and showed several important bioactivities. The separation was achieved by an Acquity UPLC BEH Symmetry Shield RP18 column (1.7 μm, 2.1 × 100 mm) column with the gradient mobile phase consisting of 5 mm ammonium acetate aqueous solution and acetonitrile. Detection was carried out by using negative‐ion electrospray tandem mass spectrometry via multiple reaction monitoring. Plasma samples were preprocessed by an extraction with ethyl acetate, and apigenin was used as internal standard. The current UPLC–MS/MS assay was validated for linearity, accuracy, intraday and interday precisions, stability, matrix effects and extraction recovery. After oral and intravenous administration, the main pharmacokinetic parameters were as follows: peak concentrations, 83.5 ± 46.2 and 1329.6 ± 343.6 ng/mL; areas under the concentration–time curve, 161.9 ± 69.7 and 264.9 ± 56.3 μg h/L; and half‐lives, 3.4 ± 0.9 and 0.3 ± 0.1 h, respectively. The absolute bioavailability in rats of protosappanin B was 12.2%. The method has been successfully applied to a pharmacokinetic and bioavailability study of protosappanin B in rats.  相似文献   

12.
Benzoylquinazolinone derivatives 3a–n were synthesized via a simple one-step reaction, and evaluated for in vitro α-glucosidase inhibitory activity. Compounds 3d , 3f–g , 3i , and 3m–n showed more inhibitory activity than standard drug acarbose (IC50 = 750.0 ± 1.5 μM), and among them, compound 3d displayed the highest α-glucosidase inhibitory activity (IC50 = 261.6 ± 0.1 μM). The kinetic analysis of the compound 3d revealed that this compound inhibited α-glucosidase in a competitive manner (Ki = 255 μM). The docking studies were applied to predict binding modes of the synthesized compounds in active site of α-glucosidase.  相似文献   

13.
Protoporphyrin IX (PpIX) produced from exogenous, orally administered 5-aminolevulinic acid (ALA) displays high tumor-selective uptake and is being successfully employed for fluorescence-guided resection (FGR) of human malignant gliomas. Furthermore, the phototoxicity of PpIX can be utilized for photodynamic therapy (PDT) of brain tumors, which has been shown previously. Here, the absolute PpIX concentration in human brain tissue was investigated following oral ALA administration (20 mg kg−1 b.w.). An extraction procedure was used to quantify PpIX in macroscopic tissue samples, weighing 0.013–0.214 g, obtained during FGR. The PpIX concentration was significantly higher in vital grade IV tumors (5.8 ± 4.8 μm , mean ± SD, range 0–28.2 μm , n = 8) as compared with grade III tumors (0.2 ± 0.4 μm , mean ± SD, range 0–0.9 μm , n = 4). There was also a large heterogeneity within grade IV tumors with PpIX displaying significantly lower levels in infiltration zones and necrotic regions as compared with vital tumor parts. The average PpIX concentration in vital grade IV tumor parts was in the range previously shown sufficient for PDT-induced tissue damage following irradiation. However, the feasibility of PDT for grade III brain tumors and for grade IV brain tumors displaying mainly necrotic tissue areas without solid tumor parts needs to be further investigated.  相似文献   

14.
This paper describes a new analytical method, using a combination of ammonium pyrrolidine dithiocarbamate/methyl isobutyl ketone (APDC‐MIBK) microextraction and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS), for the determination of the concentrations of Cd and Pb in aqueous samples. Only 200 μL of organic solvent was used throughout the entire analysis process, with enhancement factors as high as 25. Recoveries from replicate analyses of natural water [NIST 1640(a)] containing mean concentrations of 3.1 μg Cd L?1 and 9.3 μg Pb L?1 were 95 ± 3 and 104 ± 4%, respectively. The corresponding detection limits were 0.6 μg L ?1 for Cd and 0.9 μg L ?1 for Pb. The main advantage of this approach is its simplicity in terms of sample preparation, as demonstrated by quantifying the levels of Cd and Pd in real samples, including tap water, groundwater, and seawater, using a standard addition method.  相似文献   

15.
Therapeutic drug monitoring (TDM) of anti‐epileptic drugs (AED) is a routine application. Carbamazepine (CRB) is monitored as the parent drug while oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) are monitored as their active metabolite (eslicarbazepine; MHD). We have developed a UPLC‐MS/MS method for determining CRB, OXC, ESL and MHD in plasma or serum with a simplified extraction protocol. The developed method detects sildenafil (SLD), which clinically interferes with AED and is likely to be co‐administered in epileptic patients suffering from sexual insufficiency (60%). MHD was prepared in‐house. AED were simultaneously determined in presence of SLD using gatifloxacin as an internal standard (IS). Separation was achieved using acetonitrile, methanol and 100 mm ammonium acetate in water (32:3:65, v /v/v) on an Intersil®RP‐HPLC column (250 × 4.6 mm, 5 μm). A one‐step extraction was performed by simultaneous protein and phospholipids precipitation. Detection was done by tandem mass spectrometry. No relative matrix effect was observed. The method was linear (0.5–40 μg/mL for CRB, ESL and MHD and 0.05–4 μg/mL for OXC), accurate and selective. Recoveries were 64.41 ± 5.07, 45.62 ± 1.73, 61.41 ± 4.77 and 60.33 ± 1.36 for CRB, OXC, ESL and MHD, respectively. The method was successfully applied for TDM of AED.  相似文献   

16.
One new sesquineolignan, obovatalignan A ( 1 ), and one new neolignan, obovatalignan B ( 2 ), were isolated from the Magnolia obovata fruits. Their chemical structure, including absolute configuration, was determined based on various spectroscopic methods, such as HR‐EI‐MS, 1D‐NMR (1H, 13C, DEPT), 2D‐NMR (gCOSY, gHSQC, gHMBC, NOESY), and CD spectroscopy. The compounds were evaluated for protective effects against glutamate‐induced oxidative stress in HT22‐immortalized hippocampal cells and inhibitory activity against NO production in LPS‐induced RAW 264.7 cells. Compounds 1 and 2 exhibited protective effects against glutamate‐induced oxidative stress with EC50 values of 18.1 ± 1.23 and 7.10 ± 0.78 μm , respectively, as well as inhibitory effects on NO production with IC50 values of > 30.0 and 8.22 ± 2.01 μm , respectively.  相似文献   

17.
N-乙基壳聚糖的针状结晶   总被引:4,自引:0,他引:4  
在N 乙基壳聚糖的甲酸溶液浇铸膜中观察到高分子少有的针状晶体 .从球晶经后结晶得到的针状晶体为长条矩形 ,典型尺寸为~ 5 0 μm× 2~ 5 μm× 1~ 2 μm ,高分子链平行于晶体长轴 .针状晶体首先出现在球晶的核心处 ,继而出现在球晶微纤每个树枝状分叉处 ,最后才遍布球晶各处 .针状晶体可以看成是高分子伸直链结晶的一种 .浇铸膜吸潮实际上形成了超浓溶液 (浓度 >80wt% ) ,从而分子链可以运动而后结晶成针状晶体  相似文献   

18.
The preparation and validation of a number of clinical reference materials for the determination of lead in blood and urine is described. Four candidate blood lead reference materials (Lots, 047–050), and four candidate urine lead reference materials (Lots, 034, 035, 037 and 038), containing physiologically-bound lead at clinically relevant concentrations, were circulated to up to 21 selected laboratories specializing in this analysis. Results from two interlaboratory studies were used to establish certified values and uncertainty estimates for these reference materials. These data also provided an assessment of current laboratory techniques for the measurement of lead in blood and urine. For the blood lead measurements, four laboratories used electrothermal atomization AAS, three used anodic stripping voltammetry and one used both ETAAS and ICP-MS. For the urine lead measurements, 11 laboratories used ETAAS (most with Zeeman background correction) and 10 used ICP-MS. Certified blood lead concentrations, ±S.D., ranged from 5.9±0.4 μg/dl (0.28±0.02 μmol/l) to 76.0±2.2 μg/dl (3.67±0.11 μmol/l) and urine lead concentrations ranged from 98±5 μg/l (0.47±0.02 μmol/l) to 641±36 μg/l (3.09±0.17 μmol/l). The highest concentration blood lead material was subjected to multiple analyses using ETAAS over an extended time period. The data indicate that more stringent internal quality control practices are necessary to improve long-term precision. While the certification of blood lead materials was accomplished in a manner consistent with established practices, the urine lead materials proved more troublesome, particularly at concentrations above 600 μg/l (2.90 μmol/l).  相似文献   

19.
Organic nanoparticles of a fluorinated tetraphenylporphyrin (TBTPP) were produced by rapid expansion of supercritical CO(2) solutions into both air (RESS) and an aqueous receiving solution containing a stabilizing agent (RESOLV). The effect of processing conditions on both particle size and form was investigated. The size of the porphyrin nanoparticles produced via RESS increased in a well-behaved manner from 40 to 80 nm as the preexpansion temperature increased from 40 to 100 degrees C, independent of porphyrin concentration, degree of saturation, and preexpansion pressure. RESOLV of TBTPP + CO(2) solutions was investigated both for minimizing particle growth in the free jet and for the prevention of particle agglomeration. Anionic, nonionic, and polymeric stabilizing agents for the aqueous receiving solution were considered. Expansion into a 0.05 wt % SDS solution produced nanorods 50-100 nm in diameter with an aspect ratio of 3-5. RESOLV in a 0.025 wt % Pluronic F68 solution produced well-dispersed, individual, spherical nanoparticles averaging 23 +/- 10 to 32 +/- 10 nm in diameter, independent of the rapid expansion processing conditions selected. Furthermore, the resulting nanoparticle suspensions were stable, with particle sizes remaining unchanged after several months. However, some particle agglomeration occurred at higher (i.e., 1 wt % TBTPP in CO(2)) concentrations. Contact-angle measurements on solid TBTPP compacts with the tested receiving solutions indicate that a moderate wetting agent such as Pluronic F68 is most effective for preserving the size and form of the porphyrin nanoparticles produced by RESOLV. Finally, the fact that nanoparticles are produced from RESS of TBTPP, in contrast with other organics for which microparticles are produced, can be explained in terms of the high melting point of TBTPP (388 degrees C), which results in a solid-state diffusion coefficient of TBTPP low enough so that particle coalescence is significantly reduced in the free jet.  相似文献   

20.
Poly(ethylene oxide) (PEO) is known for facilitating the electrospinning of biopolymer solutions, which are otherwise not electrospinnable. The objective of this study was to improve the understanding of the positive effects of PEO on the electrospinning of whey protein isolate (WPI) solutions under different pH conditions. Alterations in protein secondary structure and polymer solution properties (viscosity, conductivity, and dynamic surface tension), as induced by pH changes, significantly affected the electrospinning behavior of WPI/PEO (10% w/w: 0.4% w/w PEO) solutions. Acidic solutions resulted in smooth fibers (707 ± 105 nm) while neutral solutions produced spheres (2.0 ± 1.0 μm) linked with ultrafine fibers (138 ± 32 nm). In comparison, alkaline solutions produced fibers (191 ± 36 nm) that were embedded with spindle‐like beads (1.0 ± 0.5 μm). 13C NMR and FTIR spectroscopies showed that the increase in random coil and α‐helix secondary structures in WPI were the main contributors to the formation of bead‐less electrospun fibers. The electrospinning‐enabling properties of PEO on aqueous WPI solutions were attributed to physical chain entanglement between the two polymers, rather than specific polymer–polymer interactions. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012  相似文献   

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