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Objective:To establish an HPLC method for the determination of isoniazid and explore the impact of 60Co-γ on the sta-bility of isoniazid. Methods:A Diamosil C18(2) column(250 mm×4.6 mm,5 μm) was used. The mobile phase consisted of metha-nol and 0.2% phosphoric acid(2 :98). The flow rate was 1.0 ml·min-1,and the detection wavelength was at 254 nm. The isonia-zid solutions at different accurate initial concentration(10,50,100 μg·ml-1,100 μg·ml-1+saturated N2,100 μg·ml-1+satu-rated O2,100 μg·ml-1+10% tert-butanol and isoniazid powder) were irradiated by 60Co-γ at different doses (0.3,0.6,1,2.5, 5,10 kGy). And then,the concentrations of remained isoniazid were determined by HPLC. Results: Isoniazid was in a good linear relationship within the range of 1-200 μg·ml-1(r=0.999 0) with the recoveriy of 98.13% (RSD=0.65%). The degradation rate of isoniazid was affected by the initial concentration and the radiation dose,which increased with the increase of absorption amount and increased with the concentration increase,and the powder almost had no degradation. The degradation of isoniazid+O2significantly de-creased,and that of isoniazid+N2and isoniazid+tert-butanol was inhibied to a certain extent. Conclusion:Isoniazid is sensitive to 60 Co-γ irradiation,and its degradation is higher with lower concentration and higher irradiation dose.
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Objective To fabricate an anti?tuberculosis controlled drug release coating with Ti?PDA?PEG?PLGA?INH and to investigate its surface characteristics, in vivo and in vitro drug release behavior, and tissue biocompatibility. Methods 4?arm?polyethylene glycol (PEG) was synthesized first. Then cover the surface of titanium (Ti) with a layer of poly dopamine (PDA) by Michael addition reaction. Use porous starch and 4?arm?PEG as a carrier, load with isoniazid (INH), then attach to the surface of titanium by casting or sol?gel dip coating methods, and then cover with a layer of poly lactic?co?glycolic acid (PLGA) by the same method, to fabricate the Ti?PDA?PEG?PLGA?INH composite coating finally. The functional group of 4?arm?PEG was charac?terized by proton nuclear resonance spectroscopy (HNMR). The surface characteristics of Ti?PDA?PEG?PLGA?INH were evaluated by scanning electron microscope (SEM), while drug release behaviors were detected by high performance liquid chromatography (HPLC) and the cumulative release rate was calculated, and carry out the antibacterial performance in vitro. The animal model of femoral condyle bone defect was established in 25 New Zealand white rabbits. Titanium rods covered with PDA?PEG?PLGA?INH coating were implanted into defect area. INH concentrations were detected by HPLC in venous blood, muscle and bone tissue at each time point postoperatively. Another 12 rabbits were randomly divided into experimental group and control group, the experi?mental group was implanted with titanium tablets and titanium rods coated with PDA?PEG?PLGA?INH in the paraspinous muscle and left femoral condyles respectively, while the control group was implanted with a blank sheet of titanium tablets and titanium rods in the same place. Hematoxylin and Eosin Staining were used to observe the biocompatibility of the composite system in vivo at 28 and 56 days postoperatively. Results Ti?PDA?PEG?PLGA?INH controlled drug release coating uniformly distributed on the surface of plates and rods, with translucent form and smooth surface. In vitro INH release kinetics exhibited a short?burst release during the first 8h, and the cumulative release of the INH was about 65%. On the 9th day, the cumulative release of the INH was about 90%, and then the release tended to be flat, and the drug release behavior in vitro continued more than 20d. In vivo release test showed that the concentration of INH in vein blood, muscle and bone tissue around the composite system was increased steadi?ly postoperatively. On about the 28th day, the concentration reached the max. However, the INH concentrations in muscle and bone tissue around the composite system were still higher than the minimum inhibitory concentration (MIC) on the 56th day. The antibacterial test in vitro showed that the titanium tablets coated with PDA?PEG?PLGA?INH formed obvious bacterial inhibition zones. The pathological results indicated that mild inflammatory reaction was seen in the 4th week postoperatively, and the reac?tive capsule formed with loose connective tissue. In the 8th week postoperatively, there's no obvious inflammation occurred, and the reactive capsule became more dense and thicker. Conclusion The study successfully fabricated the Ti?PDA?PEG?PLGA?INH anti?tuberculosis controlled drug release coating, with reasonable release behavior both in vivo and in vitro, effective antibac?terial effect of Mycobacterium tuberculosis in vitro and good tissue biocompatibility, which is a potentially effective drug delivery system for spinal tuberculosis.
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Objective:To establish an HPLC method for the simultaneous determination of chloroginic acid, baicalin and luteolin in Julan Ganmao particles. Methods:A Diamosil C18 (2) column(250 mm × 4. 6 mm,5μm) was used. The mobile phase consisted of acetonitrile and 0. 2% phosphoric acid with gradient elution. The flow rate was 1. 0 ml·min-1 , the column temperature was 35℃, and the detection wavelength was at 327 nm for chloroginic acid and baicalin, and 360 nm for luteolin. Results:Chloroginic acid, ba-icalin and luteolin was in a good linear relationship within the range of 0. 50-9. 96 μg·ml-1(r=0. 999 8), 10. 10-202. 00 μg·ml-1 (r=0.999 5), and 0.10-2.04 μg·ml-1(r=0.999 6) with the recovery of 98.13%(RSD=0.65%), 98.80%(RSD=0.26%) and 99. 62%(RSD=0. 57%), respectively. Conclusion: The developed method is simple, accurate and reliable with good repeat-ability, and can be used in the quality control of chloroginic acid, baicalin and luteolin in Julan Ganmao particles.
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Objective To investigate the effect of CYP3A5 * 3 and MDR1C3435T polymorphisms on the blood trough concentration of sirolimus in the Chinese renal transplantation recipients with stable renal function and the influencing factors for individual differences.Method 112 cases of Chinese renal transplantation recipients with stable renal function were recruited in this study.Related data of the recipients,including gender,age,height and body mass,were recoded.CYP3A5 and MDR1 genotypes were determined by the direct sequencing.Blood trough concentration of sirolimus was measured by using chemiluminescence microparticle immuno assay (CMIA).The influencing factors of individual differences in sirolimus blood trough concentration was analyzed,and the correlation of CYP3A5 * 3 and MDR1C3435T gene polymorphisms with sirolimus blood trough concentration was evaluated.Result Of the 112 cases,there were 10 cases (8.93％) of CYP3A5 * 1/* 1,49 cases (43.75％) of CYP3A5 * 1/* 3,and 53 cases (47.32％) of CYP3A5 * 3/* 3.Allele frequencies of CYP3A5 * 1 and * 3 were 30.81％ and 69.19％,respectively.There were 31 recipients (27.68％) with MDR1 3435CC,60 (53.57％) with MDR1 3435CT,and 21 (18.75％) with MDR1 3435TT.Allele frequencies for C and T at position 3435 of MDR1 were 54.46％ and 45.54％,respectively.In this study,recipients' CYP3A5 * 3 genotype was the main factor (P =0.000) of sirolimus blood trough concentration,but dose,gender,age,height,postoperative time,the level of serum creatinine,hemoglobin levels,combined use of CsA and MDR1C3435T genotype had no effects on sirolimus blood trough concentration (P ＞ 0.05).sirolimus blood trough concentration/(dose weight) in * 1/* 1,* 1/* 3 and * 3/* 3 recipients was (0.0721 ± 0.0202),(0.1055 ± 0.0395),and (0.1395 ± 0.0537) μg·L-1 ·mg-1 ·kg-1,respectively,The sirolimus blood trough concentration/ (dose weight) in * 1/* 3 recipients was 1.46 times higher than that in * 1/* 1 recipients,and that in * 3/* 3 recipients were 1.93 times higher than that in * 1/* 1 recipients.There was significant difference in sirolimus blood trough concentration/(dose weight) between recipients with different CYP3A5 * 3 genotypes (P =0.000).Conclusion The CYP3A5 * 3 gene polymorphism is closely related to the blood trough concentration/dose of sirolimus,and is the main factor of the blood trough concentration of sirolimus between individuals.
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BACKGROUND: Besides being a basic growth factor crucial to maintain and promote the development, differentiation and survival of the central nervous system, nerve growth factor(NGF) also plays an important role in the repair of injured peripheral nerves.OBJECTIVE: To investigate the effect of the muscular injection of NGF on the regeneration and functional recovery of rat sciatic nerve after crush injury.DESIGN: A randomized controlled pilot study in rats with repeated observation and measurement.SETTING: Center for new drug evaluation in a military medical university.MATERIALS: This study was performed in the Center for New Drug Evaluation, Department of Basic Medicine, Second Military Medical University during the period from July 1999 to March 2000, using 40 SD rats weighing 200 to 250 g(of either sex of half number) provided by the Sino-British SIPPR/BK Lab Aninal Ltd (Shanghai).METHODS: Forty rats were randomized into high-, mid- and low-dose NGF treatment groups, normal control group and model control group. The sciatic nerves were clamped at 6 nm distal to the sciatic notch to induce a 4-mm-wide area of crush injury. In the high-, mid-; and low-dose NGF groups, the rats were given NGF at 8, 4 and 2 μg/kg per day(corresponding to 1.6 × 10 3, 8 × 10 2 and 4 × 10 2 IU/kg per day) respectively via the muscular injection for 56 consecutive days.(NCVs) and sciatic function index(SFI) at different time points after the RESULTS: Compared with that of the model control group, the NCVs significantly increased in the high-dose NGF group 35 and 56 days after the injury,and in the mid-dose NGFgroup at 35 days(t=2.32-5.14, P ＜0.05-0.01 ). The SFIs significantly increased in all NGF-treated groups at 14 days ( t = 2. 29-6.28, P ＜ 0.05-0.01 ), with the recovery most conspicuous in high-dose NGF group; No significant difference in the SFIs was found between the NGF-treated groups on the 56th day. Morphological examination of the tissues identified no significant difference in the nerve myelin sheaths and axons in NGF-treated groups as compared with the normal control group,while in the model control group, myelin sheath dislocation with unclear microstructure was observed, accompanied by Schwann cell degeneration and necrosis.CONCLUSION: NGF promotes the repair of the damaged nerve myelin sheath and axon and stimulates nerve fiber regeneration and function recovery of the crushed rat sciatic nerves.
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OBJECTIVE:To evaluate the medical orders in terms of the medication for the inpatients with tuberculosis in our hospital.METHODS:The medical orders for the inpatients in Tuberculosis institute from Dec.7th,2007 to Jan.6th,2008 were synchronously monitored and analyzed.RESULTS:Of the total 5 592 medical orders monitored,1 461 were warned by PASS,of which,562 were warnings about drug interactions,884 about dosage and 15 were about incompatibility.CONCLUSION:Medical orders synchronously monitored by PASS could help correct and monitor the irrational medication.But the function of PASS remained to be strengthened and the data base remained to be enriched and renewed in time.