A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method...A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss. The method meets the International Conference on Harmonization guideline for analytical methods validation regarding specificity, linearity, accuracy, precision, specificity and robustness as required by health authorities and applied by industry while designing and marketing new drug products. The technique encompasses the separation of the analytes with a reverse phase C18 column under isocrafic conditions and UV detection at 272 nm and 243 nm, respectively, for theophylline and paraeetamol. The lower limit of quantification for both drugs was determined as 0.2 μg/mL and the between-batch accuracy was 99.7%. This HPLC method allows quantification of theophylline and paracetamol in milk matrices and it can be applied in the design, development and production of milk-based pediatric dosage forms.展开更多
Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) ...Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL 4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL 4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P <0.05), while cAMP and cAMP/cGMP were significantly lower than those in controls ( P <0.01). Plasma level of IL 4 was inversely correlated with forced expiratory volume at the first second (FEV 1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V 50 ) (both r =-0.46, P <0.05) while it was directly correlated with the scores of the clinical manifestations ( r =0.57, P <0.05) in COPD patients. Two weeks after treatment with theophylline, IL 4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/cGMP increased significantly ( P <0.05). The change of IL 4 was inversely correlated with the changes of FEV 1 and V 50 ( r =-0.53 and -0.54, respectively, P <0.05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL 4 might play a role in the pathoge nesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline's therapeutic effects of attenuating air flow limitation may partially depend on its anti inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL 4.展开更多
Objective: This study aimed to establish chemiluminescent immunoassay (CLIA) for quantitative determination of theophylline levels in human serum. Methods: To measure the concentration of theophylline (n=122) and eval...Objective: This study aimed to establish chemiluminescent immunoassay (CLIA) for quantitative determination of theophylline levels in human serum. Methods: To measure the concentration of theophylline (n=122) and evaluate the assay.Results: The linear range of the CLIA method was 0.51～40 mg/L (Y=1.02X+0.44, r=0.995). The intra and inter CV (coefficient variance) of CLIA were 3.20% and 3.57%, respectively. The average recovery rate was 102.3%. This method was free from interference by brilirubin (＜200 μmol/L), hemoglobin (＜10 g/L), and triglycerides (＜15 mmol/L). Conclusion: This method is simple, convenient and precise for clinical pharmacokinetics study oftheophylline.展开更多
Theophylline(TP)is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects.This study aims to improve asthma treatment by creating a dry powder inhalable(DPI)formulation ...Theophylline(TP)is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects.This study aims to improve asthma treatment by creating a dry powder inhalable(DPI)formulation of TP to be delivered directly to the lung,avoiding the side effects associated with conventional oral delivery.The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy,laser diffraction,thermal analysis and dynamic vapour sorption.Furthermore,aerosol performance was assessed using the Multi Stage Liquid Impinger(MSLI).In addition,a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells.Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery.The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70±2.59%(P<0.05)for the TP formulation containing 1.0%(w/w)sodium stearate,the most efficient for aerosolisation.Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI,results demonstrated that 56.14±7.62%of the total TP deposited(13.07±1.69μg)was transported across the Calu-3 monolayer over 180 min following deposition,while 37.05±12.62%of the deposited TP was retained in the cells.This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity.A DPI formulation of TP was developed that was shown to be suitable for inhalation.展开更多
A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric ...A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric acid(CA)in a one-step procedure.The raw materials of TP andCA,aswell as the intactTPeCA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach.The result indicates that the TPeCA cocrystal formulation was easily induced using this DSCeFTIR technique.The thermaldependent changes in three-dimensional FTIR spectral contour profiles were started from 165C to induce the co-crystal formation of TPeCA,which was prior to the endothermic peak at 173C found in the conventional DSC curve.Beyond 165C,several new IR absorption peaks at 3515,3124,1730,1710,1677,1648,1552 and 1265 cm1 corresponding to unique IR spectral peaks of intact TPeCA co-crystal were observed.The DSCeFTIR microspectroscopic results also evidenced the dimeremonomer transition of CA,but there were no markedly changes for TP or intact TPeCA co-crystal before its fusion.This strongly implies that the DSCeFTIR technique giving spectroscopic and thermodynamic information could simultaneously induce and identify the TPeCA co-crystal formation and phase transition of samples.Different storage conditions affecting the stability of both physical mixture and ground mixture of TPeCA were also determined.The physicalmixture of TPeCA after storing at 55C/75%RH condition for one day was fast transformed to TPeCA co-crystal,indicating that TPeCA co-crystal was easily induced under accelerated storage condition.While the co-crystal formed from TPeCA ground mixture was stable in both 25C/75%RH and 55C/75%RH conditions.展开更多
In the present work,the equilibrium adsorption of theophylline was studied by phenolic resin adsorbents: JDW\|2(made by ourselves) and Duolite S\|761 within a temperature range of 303\_323 K. The experimental results...In the present work,the equilibrium adsorption of theophylline was studied by phenolic resin adsorbents: JDW\|2(made by ourselves) and Duolite S\|761 within a temperature range of 303\_323 K. The experimental results show that the Freundlich adsorption law is applicable to the adsorption of theophylline on the two adsorbents,the exponents \%n\%>1 indicate that they are favorable to the adsorptions;the negative values of all the isosteric adsorption enthalpies for the theophylline indicate the exothermic process of the adsorption,while the range(10\_40 kJ/mol) of their magnitudes manifests the physisorption process;other thermodynamic properties,the free energy changes and the entropy change associated with adsorption have been calculated from the Gibbs adsorption equation and the Gibbs\|Helmholtz equation.展开更多
Theophylline has been widely used in the＇treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra-...Theophylline has been widely used in the＇treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra- tion. Because cystic fibrosis transmembrane conductance regulator（CFTR） is a cAMP-dependent Cl- channel that plays key roles in fluid secretion in vivo, we postulated that theophylline activates CFTR channel gating. We found （1） theophylline stimulated CFTR-mediated anion transport in a concentration-dependent manner, and CFTR specific blocker completely reversed the effect; （2） theophylline had no effect on △F508 or G551D mutant CFTR chloride channel activity; （3） theophylline had additive effect with forskolin（FSK） and 3-isobutyl-xanthin（IBMX）, thus a direct binding activation mechanism was suggested. In conclusion, the results may provide a clue to elucidating the molecular mechanism of theophylline activities and theophylline may present a novel lead drug in treating CFTR-related disease.展开更多
Molecular imprinting of theophylline in poly (methacrylic acid- ethylene dimethacrylate) as CEC stationary phases was synthesized by an in situ photo-initiated polymerization reaction. The effect of electrolyte pH on ...Molecular imprinting of theophylline in poly (methacrylic acid- ethylene dimethacrylate) as CEC stationary phases was synthesized by an in situ photo-initiated polymerization reaction. The effect of electrolyte pH on xanthine derivatives and the stability of MIP column performance were investigated. the relative standard deviation (D RS) of migration time of five consecutive runs on MIP column was in the range of 2.2%–3.1%. The reproducibility of migration time column to column of M(A) was in the range of 3.8%–4.9%. The highest column efficiency was more than 140 000 plates per meter. The MIP capillaries had showed better selective for theophylline, which comparing with the reference column. The urine sample was separated by spiked 5×10?4 mol·L?1 theophylline. Key words capillary electrochromatography - molecular imprinting polymers - theophylline CLC number O 657.8 Foundation item: Supported by the National Nature Science Foundation of China (20375028) and the Research Fund for the National High Technology Development “863” of China (2002AA2Z2004)Biography: Cai Ling-shuang (1968-), female, Associate professor, Ph. D, research direction: separation science.展开更多
The xanthan/chondroitin sulfate (X/CS) hydrogels, obtained by a crosslinking technique, were evaluated in vitro and in vivo as matrices for theophylline release. The influence of pH of simulated physiological media on...The xanthan/chondroitin sulfate (X/CS) hydrogels, obtained by a crosslinking technique, were evaluated in vitro and in vivo as matrices for theophylline release. The influence of pH of simulated physiological media on the X/CS swelling behaviour at 37°C was investigated. The hydrogels theophylline loading degree was evaluated by near infrared chemical imaging (NIR-CI) technique and confirmed also by FT-IR spectroscopy;the drug loading was about 77.5% based on PLS-DA prediction (Partial least squares-Discriminate Analysis). The release profiles of theophylline from X/CS hydrogels in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) depend on CS content. The release mechanisms were controlled by the drug solubility and ionic properties of the polymers. In vivo theophylline delivery was done by oral administration. Pharmacokinetic analysis revealed sustained-release characteristics for 50/50 X/CS theophylline-loaded formulation compared with raw theophylline which was rapidly absorbed, distributed and eliminated. A good in vitro-in vivo correlation was found.展开更多
7-(2-ethyltiophenyl) theophylline was used as copper corrosion inhibitor in 1M HNO3 solution. The study was performed using mass loss, scanning electron microscopy (SEM) and Density Functional Theory (DFT) methods. Th...7-(2-ethyltiophenyl) theophylline was used as copper corrosion inhibitor in 1M HNO3 solution. The study was performed using mass loss, scanning electron microscopy (SEM) and Density Functional Theory (DFT) methods. The results show that the inhibition efficiency increases up to 91.29% with increase of the inhibitor concentration (from 0.05 to 5 mM) but decreases with raising temperature of the solution. Copper dissolution was found to be temperature and 7-(2-ethyltiophenyl) theophylline concentration dependent. The thermodynamic functions related to the adsorption of the molecule on the copper surface and that of the metal dissolution were determined. The results point out a spontaneous adsorption and an endothermic dissolution processes. Adsorption models including Langmuir, El-Awady and Flory-Huggins isotherms were examined. The results also suggest spontaneous and predominant physical adsorption of 7-(2-ethyltiophenyl) theophylline on the metal surface which obeys Langmuir isotherm model. Further investigation on the morphology using scanning electron microscopy (SEM) has confirmed the existence of a protective film of inhibitor molecules on copper surface. Furthermore, the global and local reactivity parameters of the studied molecule were analyzed. Experimental and theoretical results were found to be in good agreement.展开更多
Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β...Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β-CD microspheres,which were used in treatment of asthmatic rats.At a predetermined time,the levels of eosinophil(Eos),protein,lactate dehydrogenase(LDH),aspartate transaminase(AST),glutamic pyruvic transaminase(GPT),and creatinine(Cr)were ascertained by automatic hematology and biochemical analyzers.Lung tissue histology was performed by hematoxylin-eosin staining.Results:No significant differences were found about the contents of Eos in the blood,and the contents of Eos,protein and LDH in the bronchoalveolar lavage fluid between the microsphere-treated and dexamethasone-treated groups,but the levels were lower in both treated groups than in the model group.In the microsphere-treated group,the levels of Cr,AST,and GPT in the serum of rats showed no significant differences compared with the normal group.Based on lung histopathological findings,the microspheres attenuated inflammatory cell infiltration and mucus hypersecretion compared with the model group.Conclusion:This study demonstrated that TH/CTS/β-CD microspheres exerted an anti-inflammatory effect and could serve as a novel promising drug delivery system for asthma treatment.展开更多
Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are reg...Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are regarded as a strategy for harnessing plasticity.In this work,we experimentally characterized the form II anhydrous theophylline(THPa)and its monohydrate(THPm)for their distinct plastic and elastic behaviors.Extensive DFT calculations were performed to model the effects of increasing lattice strains on molecular packing.We discovered that the energy barrier associated with the strain-induced molecular rearrangement would link to the plasticity of THPa,and possibly other simple aromatic compounds.Meanwhile,water molecules in THPm disrupt the stacking architecture from THPm and effectively undermine the general mechanism for plasticity.Hydrate formation would therefore be an alternative strategy to engineer the mechanical property of organic crystalline materials.展开更多
Background Chronic intermittent hypoxia （CIH） has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophyl...Background Chronic intermittent hypoxia （CIH） has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver. Methods Eight C57BL/6J mice were exposed to CIH for 12 weeks. Eight C57BL/6J mice were exposed to room air as a control group. Serum levels of alanine aminotransferase and aspartate aminotransferase were measured. Liver histology was observed by light and electron microscopy. Total hepatic cytochrome P450 concentration was measured. Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours. After incubation, the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated. Results CIH did not affect the serum transaminase levels. Livers from mice exposed to CIH showed hepatocellular edema, and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope. The theophylline metabolism rate was significantly inhibited by CIH compared with controls; （16.60±2.43）% vs. （21.58±4.52）% （P=0.02）. The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group; （0.83±0.08） vs. （1.13±0.21）mol/mg microsomal protein （P=0.004）. Conclusion CIH decreases theophylline metabolism by mouse hepatocytes, which may correlate with the downregulation of cytochrome P450 expression by CIH.展开更多
Objective To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breath...Objective To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients.Methods Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment.Results Patients were divided into two groups. Group Ⅰ (n =21) consisted of individuals with 15 episodes of apnea and hypopnea [as determined by the apnea-hypopnea index (AMI) ] per hour or less; Group Ⅱ (n =15, 41.7%) individuals had an index of more than 15 episodes per hour. In group Ⅱ , the AHI varied from 16. 8 to 78. 8 (42. 6 ±+15. 5) in which the obstructive AHI was 11.1 ± 8. 4 and the central AHI was 31. 5 ±9.6. Group Ⅱ had significantly more arousals (36. 8 ±21. 3 compared with 19.4 ±11.2 in group Ⅰ) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76. 7% ±4. 6% compared with 86. 5% ±2. 8%) and lower left ventricular ejection fraction (24. 2% ±8. 8% compared with 31. 5%±10. 6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4. 3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11. 3±2. 5) μg/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20. 8±13. 2 vs. 42. 6±15. 5; P < 0. 001) and the number of episodes of central apnea-hypopnea per hour (10.1 ±7. 6 vs. 31. 5±9. 6; P<0. 001). Furthermore, the percentage of total sleep time during which arterial oxyhemoglobin saturation (SaO2) was less than 90 percent (8. 8%±8. 6% vs. 23. 4% ±24.1%; P<0. 05) and the arousals per hour (18. 7 ±21. 2 vs. 36. 8 ±21. 3; P<0. 05) were also lower. There were no significant differences in the characteristics of sleep or obstructive AHI before and after theophylline treatment.Conclusions The prevalence of sleep-disordered breathing (mainly periodic respiration or cheyne-stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. In these patients, oral theophylline therapy may reduce the number of episodes of central apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal sleep.展开更多
A green,convenient,high yielding and one-pot procedure for the synthesis of novel spiro[benzo[α]pyrano[2,3-c]phenazine]derivatives by domino multi-component condensation reaction between 2-hydroxynaphthalene-l,4-dion...A green,convenient,high yielding and one-pot procedure for the synthesis of novel spiro[benzo[α]pyrano[2,3-c]phenazine]derivatives by domino multi-component condensation reaction between 2-hydroxynaphthalene-l,4-dione,benzene-l,2-diamines,ninhydrine,and malononitrile in the presence of a catalytic amount of 1,3-dimethyl-7H-purine-2,6-dione（theophylline） as an expedient,eco-friendly and reusable solid base catalyst under thermal,microwave irradiation and solvent-free conditions.This procedure has also been applied successfully for the synthesis of benzo[α]pyrano[2,3-c]phenazines.展开更多
Porous organic frameworks(POFs)are excellently stable porous materials,which can be employed as host platforms to support metal nanoparticles as functional composites for various applications.Herein,a novel POF is suc...Porous organic frameworks(POFs)are excellently stable porous materials,which can be employed as host platforms to support metal nanoparticles as functional composites for various applications.Herein,a novel POF is successfully prepared via Friedel-Crafts reaction.Silver nanoparticles(AgNPs)are embedded in the prepared POF to generate an Ag@POF composite,which not only possesses high surface area,outstanding physicochemical stability and outstretchedπ-conjugation skeleton,but also exhibits preferable electrochemical stability and conductivity.This composite is able to immobilize a mass of aptamer strands to fabricate an intriguing electrochemical aptasensor.Electrochemical impedance spectroscopy(EIS)is a commonly used technology to analyze the electrochemical signal variation.The Ag@POF-based biosensor shows the excellent electrochemical detection behavior through analyzing EIS.For instance theophylline as a research mode,the Ag@POF based electrochemical aptasensor reveals ultra-sensitiveness,high selectivity,remarkable stability,good repeatability and simple operability even in various real samples.Notably,this aptasensor has the sensitive detection performance with the limit of detection of 0.191 pg/m L(1.06 pmol/L)in a wide concentration range of 5.0×10^(-4)–5.0 ng/m L(2.78×10^(-3)–27.8 nmol/L).展开更多
OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the p...OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.展开更多
In this study, double-hydrophilic hydroxylpropyl cellulose （HPC） based copolymers with poly（N- isopropylacrylamide） （PNIPAM） and poly（acrylic acid） （PAA） as graft chains were synthesized and characterized. T...In this study, double-hydrophilic hydroxylpropyl cellulose （HPC） based copolymers with poly（N- isopropylacrylamide） （PNIPAM） and poly（acrylic acid） （PAA） as graft chains were synthesized and characterized. The release behavior of drug-loaded micelles was studied. The results show that the hydrophilicity of copolymers improves as the pH increases, whereas the hydrophobicity of copolymers enhances as the temperature increases, and all the phase behaviors are reversible. The diameter of micelles decreases and then increases with pH increase. It shows different micellizing behavior under acidic and basic conditions according to the temperature increase. In vitro release experiments, which used theophylline as a model drug, show that the micelles enhance pH sensitivity in the release process.展开更多
Chitosan and β-cyclodextrin were used to prepare microspheres with theophylline for pulmonary delivery by spray drying method. The characteristics, mucociliotoxicity, permeation rate and drug release were studied. Th...Chitosan and β-cyclodextrin were used to prepare microspheres with theophylline for pulmonary delivery by spray drying method. The characteristics, mucociliotoxicity, permeation rate and drug release were studied. The drug entrapments of microspheres Ⅰ, Ⅱ and Ⅲ were from 35.70% to 21.09% and 13.33%, while yields and encapsulation efficiencies were higher than 45% and about 90% respectively. The microspheres possessed low tap densities （0.34-0.48 g/cm^3）, appropriate diameters （3.35-3.94 μm） and theoretical aerodynamics diameters （2.20-3.04 μm）. SEM images showed the microspheres were spherical with smooth or wrinkled surface surfaces. FT-IR demonstrated theophylline had formed hydrogen bonds with chitosan and fl-cyclodextrin. The microspheres could effectively reduce the ciliotoxicity and easy to penetrate the memberine. The in vitro release of the microspheres was related to the ratio of drug/polymer and microspheres Ⅱ had a prolong release, providing the release of 72.00% in 12 h. The results suggestes that chitosan/β-cyclodextrin microspheres Ⅱ are a promising carrier as sustained release for pulmonary delivery.展开更多
It has been extensively proved that electro-acupuncture elicit analgesia in bothextensive areas and local region via supraspinal structures and spinal cord.The present investigationwas to study the role of P<sub>...It has been extensively proved that electro-acupuncture elicit analgesia in bothextensive areas and local region via supraspinal structures and spinal cord.The present investigationwas to study the role of P<sub>1</sub>-purinergic receptors in the spinal mechanisms of weak electroacupuncture-induced analgesia.Leg withdrawal latency（LWL）to noxious radiant heat focused on the ankle regionwas used to assess the effects of acupuncture and that of P<sub>1</sub>-purinergic（adenosine）receptor antago-nists,theophylline and caffeine on the electro-acupuncture（EA）analgesia.EA prolonged the LWLby 16.7%±20.3%,with an after-effect lasting about 15 min.Both theophylline and caffeineblocked the EA-induced prolongation of LWL in a dose-dependent manner at the doses of 1.6-16 mg/kg.These results suggest that P<sub>1</sub>-purinegic receptor is involved in the spinal mechanisms of weak EAproduced analgesia in the rat.展开更多
基金the financial support provided by Fundacao para a Ciência e a Tecnologia,Portugal(PTDC/DTP-FTO/1057/2012)
文摘A simple, accurate and sensitive high-performance liquid chromatography （HPLC） method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss. The method meets the International Conference on Harmonization guideline for analytical methods validation regarding specificity, linearity, accuracy, precision, specificity and robustness as required by health authorities and applied by industry while designing and marketing new drug products. The technique encompasses the separation of the analytes with a reverse phase C18 column under isocrafic conditions and UV detection at 272 nm and 243 nm, respectively, for theophylline and paraeetamol. The lower limit of quantification for both drugs was determined as 0.2 μg/mL and the between-batch accuracy was 99.7%. This HPLC method allows quantification of theophylline and paracetamol in milk matrices and it can be applied in the design, development and production of milk-based pediatric dosage forms.
文摘Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL 4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL 4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P <0.05), while cAMP and cAMP/cGMP were significantly lower than those in controls ( P <0.01). Plasma level of IL 4 was inversely correlated with forced expiratory volume at the first second (FEV 1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V 50 ) (both r =-0.46, P <0.05) while it was directly correlated with the scores of the clinical manifestations ( r =0.57, P <0.05) in COPD patients. Two weeks after treatment with theophylline, IL 4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/cGMP increased significantly ( P <0.05). The change of IL 4 was inversely correlated with the changes of FEV 1 and V 50 ( r =-0.53 and -0.54, respectively, P <0.05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL 4 might play a role in the pathoge nesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline's therapeutic effects of attenuating air flow limitation may partially depend on its anti inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL 4.
文摘Objective: This study aimed to establish chemiluminescent immunoassay (CLIA) for quantitative determination of theophylline levels in human serum. Methods: To measure the concentration of theophylline (n=122) and evaluate the assay.Results: The linear range of the CLIA method was 0.51～40 mg/L (Y=1.02X+0.44, r=0.995). The intra and inter CV (coefficient variance) of CLIA were 3.20% and 3.57%, respectively. The average recovery rate was 102.3%. This method was free from interference by brilirubin (＜200 μmol/L), hemoglobin (＜10 g/L), and triglycerides (＜15 mmol/L). Conclusion: This method is simple, convenient and precise for clinical pharmacokinetics study oftheophylline.
基金Professor Young is the recipient of an Australian Research Council Future Fellowship(project number FT110100996)Associate Professor Traini is the recipient of an Australian Research Council Future Fellowship(project number FT12010063).
文摘Theophylline(TP)is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects.This study aims to improve asthma treatment by creating a dry powder inhalable(DPI)formulation of TP to be delivered directly to the lung,avoiding the side effects associated with conventional oral delivery.The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy,laser diffraction,thermal analysis and dynamic vapour sorption.Furthermore,aerosol performance was assessed using the Multi Stage Liquid Impinger(MSLI).In addition,a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells.Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery.The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70±2.59%(P<0.05)for the TP formulation containing 1.0%(w/w)sodium stearate,the most efficient for aerosolisation.Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI,results demonstrated that 56.14±7.62%of the total TP deposited(13.07±1.69μg)was transported across the Calu-3 monolayer over 180 min following deposition,while 37.05±12.62%of the deposited TP was retained in the cells.This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity.A DPI formulation of TP was developed that was shown to be suitable for inhalation.
基金This work was supported by National Science Council,Taipei,Taiwan(NSC 100-2320-B-264-001-MY3).
文摘A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric acid(CA)in a one-step procedure.The raw materials of TP andCA,aswell as the intactTPeCA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach.The result indicates that the TPeCA cocrystal formulation was easily induced using this DSCeFTIR technique.The thermaldependent changes in three-dimensional FTIR spectral contour profiles were started from 165C to induce the co-crystal formation of TPeCA,which was prior to the endothermic peak at 173C found in the conventional DSC curve.Beyond 165C,several new IR absorption peaks at 3515,3124,1730,1710,1677,1648,1552 and 1265 cm1 corresponding to unique IR spectral peaks of intact TPeCA co-crystal were observed.The DSCeFTIR microspectroscopic results also evidenced the dimeremonomer transition of CA,but there were no markedly changes for TP or intact TPeCA co-crystal before its fusion.This strongly implies that the DSCeFTIR technique giving spectroscopic and thermodynamic information could simultaneously induce and identify the TPeCA co-crystal formation and phase transition of samples.Different storage conditions affecting the stability of both physical mixture and ground mixture of TPeCA were also determined.The physicalmixture of TPeCA after storing at 55C/75%RH condition for one day was fast transformed to TPeCA co-crystal,indicating that TPeCA co-crystal was easily induced under accelerated storage condition.While the co-crystal formed from TPeCA ground mixture was stable in both 25C/75%RH and 55C/75%RH conditions.
文摘In the present work,the equilibrium adsorption of theophylline was studied by phenolic resin adsorbents: JDW\|2(made by ourselves) and Duolite S\|761 within a temperature range of 303\_323 K. The experimental results show that the Freundlich adsorption law is applicable to the adsorption of theophylline on the two adsorbents,the exponents \%n\%>1 indicate that they are favorable to the adsorptions;the negative values of all the isosteric adsorption enthalpies for the theophylline indicate the exothermic process of the adsorption,while the range(10\_40 kJ/mol) of their magnitudes manifests the physisorption process;other thermodynamic properties,the free energy changes and the entropy change associated with adsorption have been calculated from the Gibbs adsorption equation and the Gibbs\|Helmholtz equation.
基金Supported by the Program for New Century Excellent Talents in University of China(No.NCET-07-0406)the Program for Excellent Talents in University of Liaoning Province,China(No.2006R33)+1 种基金Changchun Municipal Science and Technology Fund (No.2007sf19)Project of General Administration of Quality Supervision of China(No.2006IK145)
文摘Theophylline has been widely used in the＇treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra- tion. Because cystic fibrosis transmembrane conductance regulator（CFTR） is a cAMP-dependent Cl- channel that plays key roles in fluid secretion in vivo, we postulated that theophylline activates CFTR channel gating. We found （1） theophylline stimulated CFTR-mediated anion transport in a concentration-dependent manner, and CFTR specific blocker completely reversed the effect; （2） theophylline had no effect on △F508 or G551D mutant CFTR chloride channel activity; （3） theophylline had additive effect with forskolin（FSK） and 3-isobutyl-xanthin（IBMX）, thus a direct binding activation mechanism was suggested. In conclusion, the results may provide a clue to elucidating the molecular mechanism of theophylline activities and theophylline may present a novel lead drug in treating CFTR-related disease.
文摘Molecular imprinting of theophylline in poly (methacrylic acid- ethylene dimethacrylate) as CEC stationary phases was synthesized by an in situ photo-initiated polymerization reaction. The effect of electrolyte pH on xanthine derivatives and the stability of MIP column performance were investigated. the relative standard deviation (D RS) of migration time of five consecutive runs on MIP column was in the range of 2.2%–3.1%. The reproducibility of migration time column to column of M(A) was in the range of 3.8%–4.9%. The highest column efficiency was more than 140 000 plates per meter. The MIP capillaries had showed better selective for theophylline, which comparing with the reference column. The urine sample was separated by spiked 5×10?4 mol·L?1 theophylline. Key words capillary electrochromatography - molecular imprinting polymers - theophylline CLC number O 657.8 Foundation item: Supported by the National Nature Science Foundation of China (20375028) and the Research Fund for the National High Technology Development “863” of China (2002AA2Z2004)Biography: Cai Ling-shuang (1968-), female, Associate professor, Ph. D, research direction: separation science.
文摘The xanthan/chondroitin sulfate (X/CS) hydrogels, obtained by a crosslinking technique, were evaluated in vitro and in vivo as matrices for theophylline release. The influence of pH of simulated physiological media on the X/CS swelling behaviour at 37°C was investigated. The hydrogels theophylline loading degree was evaluated by near infrared chemical imaging (NIR-CI) technique and confirmed also by FT-IR spectroscopy;the drug loading was about 77.5% based on PLS-DA prediction (Partial least squares-Discriminate Analysis). The release profiles of theophylline from X/CS hydrogels in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) depend on CS content. The release mechanisms were controlled by the drug solubility and ionic properties of the polymers. In vivo theophylline delivery was done by oral administration. Pharmacokinetic analysis revealed sustained-release characteristics for 50/50 X/CS theophylline-loaded formulation compared with raw theophylline which was rapidly absorbed, distributed and eliminated. A good in vitro-in vivo correlation was found.
文摘7-(2-ethyltiophenyl) theophylline was used as copper corrosion inhibitor in 1M HNO3 solution. The study was performed using mass loss, scanning electron microscopy (SEM) and Density Functional Theory (DFT) methods. The results show that the inhibition efficiency increases up to 91.29% with increase of the inhibitor concentration (from 0.05 to 5 mM) but decreases with raising temperature of the solution. Copper dissolution was found to be temperature and 7-(2-ethyltiophenyl) theophylline concentration dependent. The thermodynamic functions related to the adsorption of the molecule on the copper surface and that of the metal dissolution were determined. The results point out a spontaneous adsorption and an endothermic dissolution processes. Adsorption models including Langmuir, El-Awady and Flory-Huggins isotherms were examined. The results also suggest spontaneous and predominant physical adsorption of 7-(2-ethyltiophenyl) theophylline on the metal surface which obeys Langmuir isotherm model. Further investigation on the morphology using scanning electron microscopy (SEM) has confirmed the existence of a protective film of inhibitor molecules on copper surface. Furthermore, the global and local reactivity parameters of the studied molecule were analyzed. Experimental and theoretical results were found to be in good agreement.
基金the foundation for visiting scholar abroad in Weifang Medical University,National Natural Science Foundation of China(No.81973671,81774125)Weifang Science and Technology Development Plan Project(2018YX060).
文摘Objective:This study aimed to investigate the effects of TH/CTS/β-CD microspheres by oral administration on ovalbumin allergic asthma of a rat model.Methods:Spray drying method was applied for preparing the TH/CTS/β-CD microspheres,which were used in treatment of asthmatic rats.At a predetermined time,the levels of eosinophil(Eos),protein,lactate dehydrogenase(LDH),aspartate transaminase(AST),glutamic pyruvic transaminase(GPT),and creatinine(Cr)were ascertained by automatic hematology and biochemical analyzers.Lung tissue histology was performed by hematoxylin-eosin staining.Results:No significant differences were found about the contents of Eos in the blood,and the contents of Eos,protein and LDH in the bronchoalveolar lavage fluid between the microsphere-treated and dexamethasone-treated groups,but the levels were lower in both treated groups than in the model group.In the microsphere-treated group,the levels of Cr,AST,and GPT in the serum of rats showed no significant differences compared with the normal group.Based on lung histopathological findings,the microspheres attenuated inflammatory cell infiltration and mucus hypersecretion compared with the model group.Conclusion:This study demonstrated that TH/CTS/β-CD microspheres exerted an anti-inflammatory effect and could serve as a novel promising drug delivery system for asthma treatment.
基金supported by the Young Scientists Promotion Fund of Natural Science Foundation of Guangdong Province,National Natural Science Foundation of China(No.81703438)the Key R&D Program of Shandong Province(No.2021ZDSYS26)National Science and Technology Major Project of China(No.2018ZX09711001-001-013)+1 种基金CAMS Innovation Fund for Medical Sciences(No.2017-I2M-3-010)Student Innovation Training Program(No.201812121093)。
文摘Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances.Analogous to metals,the identifications of molecular slip planes in organic crystals are regarded as a strategy for harnessing plasticity.In this work,we experimentally characterized the form II anhydrous theophylline(THPa)and its monohydrate(THPm)for their distinct plastic and elastic behaviors.Extensive DFT calculations were performed to model the effects of increasing lattice strains on molecular packing.We discovered that the energy barrier associated with the strain-induced molecular rearrangement would link to the plasticity of THPa,and possibly other simple aromatic compounds.Meanwhile,water molecules in THPm disrupt the stacking architecture from THPm and effectively undermine the general mechanism for plasticity.Hydrate formation would therefore be an alternative strategy to engineer the mechanical property of organic crystalline materials.
文摘Background Chronic intermittent hypoxia （CIH） has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver. Methods Eight C57BL/6J mice were exposed to CIH for 12 weeks. Eight C57BL/6J mice were exposed to room air as a control group. Serum levels of alanine aminotransferase and aspartate aminotransferase were measured. Liver histology was observed by light and electron microscopy. Total hepatic cytochrome P450 concentration was measured. Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours. After incubation, the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated. Results CIH did not affect the serum transaminase levels. Livers from mice exposed to CIH showed hepatocellular edema, and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope. The theophylline metabolism rate was significantly inhibited by CIH compared with controls; （16.60±2.43）% vs. （21.58±4.52）% （P=0.02）. The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group; （0.83±0.08） vs. （1.13±0.21）mol/mg microsomal protein （P=0.004）. Conclusion CIH decreases theophylline metabolism by mouse hepatocytes, which may correlate with the downregulation of cytochrome P450 expression by CIH.
基金a grant from the Hubei Provincial Science Foundation of Science & Technology Department ( No. 981P1605).
文摘Objective To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients.Methods Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment.Results Patients were divided into two groups. Group Ⅰ (n =21) consisted of individuals with 15 episodes of apnea and hypopnea [as determined by the apnea-hypopnea index (AMI) ] per hour or less; Group Ⅱ (n =15, 41.7%) individuals had an index of more than 15 episodes per hour. In group Ⅱ , the AHI varied from 16. 8 to 78. 8 (42. 6 ±+15. 5) in which the obstructive AHI was 11.1 ± 8. 4 and the central AHI was 31. 5 ±9.6. Group Ⅱ had significantly more arousals (36. 8 ±21. 3 compared with 19.4 ±11.2 in group Ⅰ) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76. 7% ±4. 6% compared with 86. 5% ±2. 8%) and lower left ventricular ejection fraction (24. 2% ±8. 8% compared with 31. 5%±10. 6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4. 3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11. 3±2. 5) μg/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20. 8±13. 2 vs. 42. 6±15. 5; P < 0. 001) and the number of episodes of central apnea-hypopnea per hour (10.1 ±7. 6 vs. 31. 5±9. 6; P<0. 001). Furthermore, the percentage of total sleep time during which arterial oxyhemoglobin saturation (SaO2) was less than 90 percent (8. 8%±8. 6% vs. 23. 4% ±24.1%; P<0. 05) and the arousals per hour (18. 7 ±21. 2 vs. 36. 8 ±21. 3; P<0. 05) were also lower. There were no significant differences in the characteristics of sleep or obstructive AHI before and after theophylline treatment.Conclusions The prevalence of sleep-disordered breathing (mainly periodic respiration or cheyne-stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. In these patients, oral theophylline therapy may reduce the number of episodes of central apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal sleep.
基金financial support from the Research Council of the University of Sistan and Baluchestan and Islamic Azad University of Yazd
文摘A green,convenient,high yielding and one-pot procedure for the synthesis of novel spiro[benzo[α]pyrano[2,3-c]phenazine]derivatives by domino multi-component condensation reaction between 2-hydroxynaphthalene-l,4-dione,benzene-l,2-diamines,ninhydrine,and malononitrile in the presence of a catalytic amount of 1,3-dimethyl-7H-purine-2,6-dione（theophylline） as an expedient,eco-friendly and reusable solid base catalyst under thermal,microwave irradiation and solvent-free conditions.This procedure has also been applied successfully for the synthesis of benzo[α]pyrano[2,3-c]phenazines.
基金financially supported by the National Natural Science Foundation of China(No.21801187)。
文摘Porous organic frameworks(POFs)are excellently stable porous materials,which can be employed as host platforms to support metal nanoparticles as functional composites for various applications.Herein,a novel POF is successfully prepared via Friedel-Crafts reaction.Silver nanoparticles(AgNPs)are embedded in the prepared POF to generate an Ag@POF composite,which not only possesses high surface area,outstanding physicochemical stability and outstretchedπ-conjugation skeleton,but also exhibits preferable electrochemical stability and conductivity.This composite is able to immobilize a mass of aptamer strands to fabricate an intriguing electrochemical aptasensor.Electrochemical impedance spectroscopy(EIS)is a commonly used technology to analyze the electrochemical signal variation.The Ag@POF-based biosensor shows the excellent electrochemical detection behavior through analyzing EIS.For instance theophylline as a research mode,the Ag@POF based electrochemical aptasensor reveals ultra-sensitiveness,high selectivity,remarkable stability,good repeatability and simple operability even in various real samples.Notably,this aptasensor has the sensitive detection performance with the limit of detection of 0.191 pg/m L(1.06 pmol/L)in a wide concentration range of 5.0×10^(-4)–5.0 ng/m L(2.78×10^(-3)–27.8 nmol/L).
基金the Deanship of Scientific Research at King Saud University for funding this research group,No. RG-1435-041
文摘OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.
文摘In this study, double-hydrophilic hydroxylpropyl cellulose （HPC） based copolymers with poly（N- isopropylacrylamide） （PNIPAM） and poly（acrylic acid） （PAA） as graft chains were synthesized and characterized. The release behavior of drug-loaded micelles was studied. The results show that the hydrophilicity of copolymers improves as the pH increases, whereas the hydrophobicity of copolymers enhances as the temperature increases, and all the phase behaviors are reversible. The diameter of micelles decreases and then increases with pH increase. It shows different micellizing behavior under acidic and basic conditions according to the temperature increase. In vitro release experiments, which used theophylline as a model drug, show that the micelles enhance pH sensitivity in the release process.
基金the National Natural Science Foundation of China(No.30670566)Natural Science Foundation of Shandong Province
文摘Chitosan and β-cyclodextrin were used to prepare microspheres with theophylline for pulmonary delivery by spray drying method. The characteristics, mucociliotoxicity, permeation rate and drug release were studied. The drug entrapments of microspheres Ⅰ, Ⅱ and Ⅲ were from 35.70% to 21.09% and 13.33%, while yields and encapsulation efficiencies were higher than 45% and about 90% respectively. The microspheres possessed low tap densities （0.34-0.48 g/cm^3）, appropriate diameters （3.35-3.94 μm） and theoretical aerodynamics diameters （2.20-3.04 μm）. SEM images showed the microspheres were spherical with smooth or wrinkled surface surfaces. FT-IR demonstrated theophylline had formed hydrogen bonds with chitosan and fl-cyclodextrin. The microspheres could effectively reduce the ciliotoxicity and easy to penetrate the memberine. The in vitro release of the microspheres was related to the ratio of drug/polymer and microspheres Ⅱ had a prolong release, providing the release of 72.00% in 12 h. The results suggestes that chitosan/β-cyclodextrin microspheres Ⅱ are a promising carrier as sustained release for pulmonary delivery.
文摘It has been extensively proved that electro-acupuncture elicit analgesia in bothextensive areas and local region via supraspinal structures and spinal cord.The present investigationwas to study the role of P<sub>1</sub>-purinergic receptors in the spinal mechanisms of weak electroacupuncture-induced analgesia.Leg withdrawal latency（LWL）to noxious radiant heat focused on the ankle regionwas used to assess the effects of acupuncture and that of P<sub>1</sub>-purinergic（adenosine）receptor antago-nists,theophylline and caffeine on the electro-acupuncture（EA）analgesia.EA prolonged the LWLby 16.7%±20.3%,with an after-effect lasting about 15 min.Both theophylline and caffeineblocked the EA-induced prolongation of LWL in a dose-dependent manner at the doses of 1.6-16 mg/kg.These results suggest that P<sub>1</sub>-purinegic receptor is involved in the spinal mechanisms of weak EAproduced analgesia in the rat.
