A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

Preparation for Polyvinyl Alcohol Hollow Microsphere and Its Sustained Release Effect on Urea

[Objective] The aim of this study was to discuss the optimizing preparation conditions of polyvinyl alcohol(PVA)hollow microsphere and its application in the production of slow-release urea fertilizer.[Method]PVA hollow microsphere was prepared by the emulsion chemical cross-linking method,while its composition,morphology and particle size was analyzed by technologies of FT-IR,SEM and TEM respectively.Thus,factors such as rate of emulsified speed,crosslink temperature and linking agent amount with effects on morphology and particle size of hollow microsphere were also discussed in this study.Furthermore,based on the optimizing preparation conditions,PVA fertilizer carrier microsphere was prepared by coating urea to investigate its sustained release effect on urea.[Result]The optimizing preparation conditions of polyvinyl alcohol(PVA)hollow microsphere were as follows:rate of emulsified speed 6 000 r/min,crosslink temperature 35 ℃ and linking agent amount 25 ml.PVA fertilizer carrier microsphere had significant sustained release effect on urea,and the optimal cross-linking time was 3 hours.[Conclusion]This study provides theoretical basis for the development of new slow-release fertilizer.

Effects of long-term sustained naltrexone release on the optic center in opioid-dependent patients Case-control study in four provinces of China

Very little is known about visual functional recovery following long-term naltrexone administration in opioid-dependent patients. In the present study, a portable event-related potential （ERP） working system was utilized to collect and record ERP in opioid-dependent patients and normal controls in visual half-field testing. In addition, the influence of long-term sustained naltrexone release on the visual nervous system was observed in opioid-dependent patients. Results revealed a significant main group effect in reaction time to visual signal stimulations. The reaction time of normal controls was shortest, but longest in opioid-dependent patients. The reaction time of long-term sustained naltrexone release group and compulsory detoxification group was similar to normal controls. A significant main group effect was also observed in P100 latency, and P100 latency in normal controls and the compulsory detoxification group was significantly decreased compared with the opioid-dependent patients. P100 amplitude at the Oz-electrode resulted in a significant main group effect. In particular, normal controls exhibited significant differences compared with long-term sustained release naltrexone and compulsory detoxification groups. These findings demonstrated that long-term sustained naltrexone release effectively ameliorated optic center function and improved visual sensitivity and reactions in opioid-dependent patients.

Migration and Transformation of Coated Controlled Release Nitrogen in Soil under Co-situs Application Mode

By using field trials, the migration and transformation of coated controlled release nitrogen （YZS80） in soil under the co-situs application mode were studied. The results indicated that YZS80 nitrogen dissolved out in average speed of about 0.4%/d and 32% totally in 80 d compared with common compound fertUizer. For YZS80, in the vertical downward direction of application points, urea nitrogen content increased significantly （P 〈0.05） in the 45 -80 d and the 30 -60 cm soil layers; nitrate nitrogen content was little change range and in moderate （10 -100 mg/kg） in 0 -80 d and 10 -60 cm soil layers, but increased significantly （ P 〈0.05） 45 -80 d compared to 0 -45 d; ammonium nitrogen content was significant lower （P〈0.05） before 45 d in 10 -30 cm soil layers, but significant higher（P〈0.05） after 45 d in 10 -60 cm soil layers; NO3^- -N/NH4^＋ -N meets gradually the needs of the crop with the extension of time. Under the co-situs application mode, the possibility of burning root and salt injury and loss dsk of nitrate leaching is a significant reduction.

Effect of Slow and Controlled Release Fertilizers on the Yield and Nutrient Use Efficiency of Hot Pepper in Qiu-bei

[Objective] The aim of this study was to investigate the impacts of slow and controlled release fertilizers（SCRF）on the yield of qiubei hot pepper,its nutrient use efficiency and environment.[Method] Using Qiubei hot pepper（Capsicum frutescens L.）as the experimental material,we studied the fertilization effect and environment-protecting effect of SCRF.[Result] The result showed that SCRF could improve the agronomic characteristics of hot pepper.Compared to singly applied common fertilizers,SCRF increased economic yield by 20.90% and economic benefit by 13 234.35 Yuan/hm2,and the ratio of output to input was improved by 47.93%.In comparison with common straight fertilizers at same NPK proportion and rate,SCRF increased economic yield by 5.26% and economic benefit by 5 554.80 Yuan/hm2,and the ratio of output to input was improved by 9.91%.Under the reduced use of SCRF by 20%,SCRF increased economic yield by 12.38% and economic benefit by 9595.20 Yuan/hm2 compared with singly applied common fertilizers,and the ratio of output to input was improved by 65.95%.SCRF improved nitrogen,phosphorus and potassium use efficiencies by 12.42-17.53,3.35-5.24 and 5.37-14.02 percents respectively.[Conclusion] As the result of much reduced N and P application rates,SCRF would significantly economize fertilizer resources and minimize the pollution caused by the loss of fertilizer nutrients,which is of practical importance for environment protection.

Evaluation of Control Effects against Sugarcane Pests：A New Sustained-release and Long-lasting Pesticide and Convenient and Efficient Pesticide Application Technology

[Objective]The paper was to screen a new ideal sustained-release,long-lasting and low-toxic pesticide and convenient and efficient pesticide application technology for controlling Ceratovacuna lanigera and Baliathrips serratus. [Method]2% Imidacloprid GR were selected and applied in the soil for field efficacy trial. [Result] The optimum dosage of 2% imidacloprid GR was 30 kg/hm^2（ active ingredient 600 g）,which can be mixed with fertilizer（ 30 kg pesticide and 40-80 kg fertilizer per hm^2） once combined with sugarcane planting management or big ridging during February and June. The control effects against C. lanigera and B. serratus could be more than 98. 2% and 81. 1%,respectively. The actual yield and sugar content in various pesticide treatments were increased by 33 390 kg/hm^2 and 6. 6% respectively compared to blank control. [Conclusion]2% imidacloprid GR has good control effects on C. lanigera and B. serratus. It is a new pesticide with ideal sustained-release,long-lasting and low-toxin effects against C. lanigera and B. serratus. Therefore,it could be used alternatively with other pesticides,to delay production and development of drug resistance.

Effects of a New Long-term Controlled-release Fertilizer on Growth and Development and Yield of Summer Maize

[Objective] The aim was to select the optimal amount of controlled-release fertilizer and provide theoretical references for controlled-release fertilizers use in summer maize. [Method] Long-term controlled-release fertilizers were applied once at sowing summer maize to explore effects on maize growth, yield, economic profits and environment. [Result] Maize yield reduced a little in the treatment group with 60% CRF, and increased in varying degrees in the rest groups in the range of 1.1%-7.4%, and some showed significant differences. [Conclusion] Controlled-release fertilizers can be applied once at the amount of 80% common fertilizer＇s, with con- sideration of maize yield, nitrogen use rate and economic profits, which is beneficial for summer maize application and promotion in North China.

Nitrogen recovery and nitrate leaching of controlled release nitrogen fertilizer in irrigated paddy soil

Ordinary high nitrogen fertilizer often results in nitrate (NO3--N) leaching and low recovery. Microplot and field plot experiments were conducted to determine the effect of controlled release nitrogen fertilizer (CRNF) on reco very and nitrate leaching on paddy soils. During two early rice cropping seasons (2002 and 2003), a single basal application of CRNF at 90 kg N ha-1 increased grain yields by 7.7%to 11.6%compared with two applications of urea. Estimated by the difference method fertilizer N recovery of CRNF (mean 76.3%) was 38.9 pe rcentage point higher than that of urea (mean 37.4%); estimated by 15N isotope method (mean 49.6%) CRNF (mean 67.1%) was 35.9 percentage point higher than ur ea (mean 31.2%). NO3--N leaching losses were 9.19 and 6.70 kg ha-1 for urea and CRNF, respectively. NO3--N leaching during the early rice cropping season was 27.1 %lower from CRNF than from two applications of urea. These losses repr esent 10.2%and 7.4%of applied urea-N and CRNF-N. Results from this study ind icate that CRNF improves N recovery and reduces NO3--N leaching and increases rice yield.

Effects of the Application of Controlled Release Nitrogen Fertilizer on Rapeseed Yield, Agronomic Characters and Soil Fertility

In order to study the effects of controlled release nitrogen fertilizer （CRNF） application on rapeseed, a simulated experiment was carried out with 3 types of paddy soils in Dongting Lake area for 4 consecutive years of applying CRNF under double rice cropping system after planting rapeseed crop in the fallow season. The effects of CRNF application on rapeseed yield, agronomic characters and soil fertility were studied in this paper. The results showed that CRNF application improved the growth of rapeseed plant and increased rapeseed yield of CRNF treatments in the purple calcareous clayed paddy soil （PCS） and alluvial loamy paddy soil （ALS） which respectively increased by 12.2% and 9.8% compared with applying urea, re- spectively. The rapeseed yield in 70% CRNF treatment obviously decreased com- pared with urea treatment. The contents of available N and organic carbon in soil increased by 25.0% and 3.2% in CRNF treatment in the ALS after rapeseed crop, respectively; and available N increased by 13.5% in the PCS. Both rapeseed yield and soil fertility in CRNF treatment and 70% CRNF treatment were lower than those in CK treatment in the reddish yellow clayed paddy soil （RYS）. The results al- so indicated that the functions of CRNF application on rapeseed yield increase and soil nitrogen fertility improvement were very obvious in the PCS and ALS.

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Effects of Controlled Release Fertilizer on Loss of Nitrogen and Phosphorus from Farmland

[Objective] The aim was to study on effects of controlled release fertilizer on loss of nitrogen and phosphorus from farmland. [Method] Experiment was conducted in fields planted with rice and corn around Chao Lake and effects of compound fertilizer, controlled release fertilizer and controlled release fertilizer （reduced by 20%） on loss of nitrogen and phosphorus through runoff and leaching were analyzed. [Result] Loss of nitrogen and phosphorus mainly occurred in early stage of fertilizing; loss caused by runoff accounted for over 98% and caused by leaching was lower than 2%, indicating that nutrients of rice and corn mainly lost through runoff. As for controlled release fertilizers with 20% reduced, total loss of N and P decreased by 60% and 63% in rice field and reduced by 27.8% and 34% in corn field, respectively, indicating that controlled release fertilizer would maintain nutrients in soils high in later period of plant growth, improve use efficiency of N and P, reduce N and P loss in rice and corn fields in rainy season, and decrease non-point pollution. [Conclusion] The research suggested that controlled release fertilizer would slow down the loss of nutrients in farmlands, providing scientific references and technological support for extension of controlled release fertilizer and reduction of agricultural non-point pollution.

Effect of Controlled Release Nitrogen on Wheat Growth and Yield

[Objective] Effects of controlled release N fertilizers on wheat growth and yield were studied to provide reference for the application of controlled release fertilizers on wheat. [Method] A field experiment was conducted to study the effects of different types and levels of controlled release N fertilizers on the growth and yield of wheat. In this experiment, a treatment with the application of common urea and potassium chloride（common fertilizer） was established, and treatments with controlled release N fertilizers A and B with different coating materials were also established. [Result] The results showed that under the condition of the same P and K levels, controlled release N fertilizer A at a proportion of 100%, controlled release N fertilizer A at a proportion of 80% and controlled release N fertilizer B at a proportion of 80% could promote wheat growth, optimize yield components, and increase the amount of dry matter accumulation and grain yield. [Conclusion] One-time application of controlled release N fertilizer could be adopted in wheat production to achieve the purposes of saving fertilizer, saving labor and increasing efficiency.

Effects of Controlled Release Nitrogen Fertilizer on Seedling Growth and Nutrient Uptake of Bitter Gourd

Different application rates of controlled release nitrogen fertilizer （CRFN） were designed to evaluate their effects on the growth and root morphology of bitter gourd （Momordica charantia L.） seedlings, and thus determine the optimal nitrogen amount and suitable nitrogen content in substrate at seedling transplanting,, in com- parison with conventional fertilizer application. CRFN was applied at five levels, 0, 0.6, 1.2, 2.4 and 4.8 kg N/m3, and conventional fertilizer was applied at 0.6 kg N/m3 as control. Four replicates were included in each treatment. The results showed that 0.6-2.4 kg N/m3 CRFN provided sufficient N nutrient for bitter gourd, with higher shoot and root dry weights, root length and root surface area than control treat- ments. Correspondingly, the total inorganic nitrogen in substrate ranged from 99.3 to 162.5 mg/pot at seedling transplanting in these treatments. 1.2 kg N/m3 was proven to be the optimal CRFN rate. Compared with conventional nitrogen fertilizer applica- tion, 1.2 kg N/m3 CRFN in substrate increased the dry weight, nitrogen uptake and improved root morphology indices of seedlings, and more than 83.3 mg/pot inorgan- ic nitrogen could be carried with substrate at transplanting, revealing a potential to reduce N-deficient risk after rain and basal N input by continuous release of CRFN.

Effects of Gel-based Controlled Release Fertilizers on Agronomic Characteristics and Physiological Indices of Corn

[Objective] This study aimed to investigate the effects of gel-based controlled release fertilizers （CRFs） on agronomic characteristics and physiological indices of corn. [Method] Pot experiment was carried out to investigate the agronomic characteristics and physiological indices of corn fertilized with controlled release fertilizers compared with conventional fertilizer （CF）. [Result] Plant height, stem girth, leaf area and root volume of corn were significantly increased under the CRF treatments; photosynthetic rate and soluble protein content were also improved. Dry matter accumulations under the two CRF treatments were increased by 21.3% and 17.0% compared with CF application at one time （CF1）, and 19.6% and 15.4% with CF application at two times （CF2）, respectively. Accumulation amounts of N, P and K in whole plant under the two CRF treatments were increased by 44.0% -24.7% , 40.0%-25.9% and 20.1% -13.9% ; and the nutrient use efficiencies of N, P and K were improved by 22.9% -13.4% , 11.2% -9.6% and 17.5% -12.1% , respectively. [Conclusion] The results implied that the CRFs could significantly improve nutrient use efficiency and plant yield.

Study of Sustained Release Phenylpropanolamine Hydrochloride Hydrophilic Matrix Tablets Containing Hydroxypropylmethylcellulose K100M and Carbopol 971P

选用HPMC K100M和卡波普971P为骨架材料，粉末直接压片法制备骨架片，考察释放度，反相高效液相色谱法检测盐酸苯丙醇胺（PPA·HCl）的浓度。释药曲线均符合Higuchi方程（R＞0．98，P＜0．01）。运用正交设计法，以美国市场的PPA·HCl缓释片Acutrim^R为对照，相似因子f2值为指标，筛选获得了最优处方。其工艺重现性合格。研制片在0．1mol·L^-1 HCl,H2O(pH6.5)，磷酸盐缓冲液（PBS）pH5.0,6.8和7.4的介质中，以及在0.1mol·L^-1HCl中释放2h，转移至PBS6．8中释放10h，相对于对照品的f2值为63－74，表明在各介质中两制剂的释药曲线相似。释药影响因素的考察结果表明：在本实验考察的范围内，骨架片在水中的释药速率与HPMC K100M和卡波普971P的用量呈负相关。HPMC K100M和卡波普971P的比例（保持聚合物总用量相同），硬脂酸镁量和骨架片硬度对释药速率无显著性影响。

Pharmacokinetics of Moclobemide Sustained Release Tablets after Multiple Oral Dose Administration in Healthy Volunteers

To investigate the pharmacokinetic characteristics of moclobemide sustainedrelease tablets after multiple oral dose administration in healthy Chinese volunteers. MethodsMoclobemide sustained release tablets were given as a multiple oral dose regimen of 300 mg oncedaily for five consecutive days to 12 healthy volunteers. The concentrations of moclobemide inplasma were determined by reversed-phase high performance liquid chromatography. The partialpharmacokinetic parameters were calculated using 3p97 pharmacokinetic program. Results Theconcentration-time profile fitted an one-compartment model best. The steady-state pharmacokineticparameters of moclobemide sustained release tablets after multiple oral doses were as follows:C_(max) was (1 950 +- 156) μg· L^(-1), T_(max) was (6.00 +-1.55) h, T_(1/2(kel)) was (3.14 +-0.12)h, AUC_(ss 0-24) was (22 836 +- 1 842) μg·h· L^(-1), MRT was (7.68+-0.36) h, CL/F_((s)) was(20.2+-2.1) L·h^(-1), and V/F_((c)) was (91.4+-9.4) L, respectively. No marked adverse events werenoted during this study. Conclusion The formulation has a sustained-release effect and goodtolerance in the healthy volunteers, which provides useful information for clinical practice.

Effect of Continuous Application of Controlled Release Nitrogen Fertilizer in Various Types of Soil in Dong-Ting Lake Region under Double Rice Cropping System

[Objective] This study aimed to explore the effects of continuous application of controlled release nitrogen fertilizer under double rice cropping system. [Method] By modeling three types of paddy soils in Dong-Ting Lake area, four treatments as no fertilizer （CK）, urea, controlled release nitrogen fertilizer （CRNF） and 70% controlled release nitrogen fertilizer （70% CRNF） were designed in the micro-plot trials from 2005 to 2008. [Result] The rice yield in treatment CRNF at N 150 kg/hm2 was increased by 10.3%, 8.0% and 2.4% compared with treatment of urea, in alluvial sandy loamy paddy soil （ALS）, purple calcareous clayey paddy soil （PCS）, and reddish yellow loamy paddy soil （RYS）, respectively; and the yield in treatment of 70% CRNF was increased by 6.1%, 2.6% and -0.8%, respectively. The ranking order of nitrogen uptake amount by plant in early rice and late rice was CRNF 70% CRNF urea CK in all three types of soil. Nitrogen utilization efficiency of CRNF in above three types of soil was 60.7%, 59.6% and 56.3%, increased by 23.8%, 19.4% and 16.3% compared with that in treatment of urea, respectively. Nitrogen utilization efficiency of CRNF in early rice was increased year by year, and was higher than that of 70% CRNF during the whole experiment stage, while that in late rice was increased first and then decreased from the 3rd year. [Conclusion] Continuous application CRNF could alleviate the decreasing of soil nitrogen fertility and organic carbon especially in ALS, increase rice yield and nitrogen utilization efficiency in double-rice cropping system.

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

Sustained release Eudragit RL/RS microspheres encapsulating nifedipine were prepared using the acetone/liquid paraffin emulsion solvent evaporation method. The influence of different preparation factors on release of the drug in vitro was investigated. The release rate of nifedipine from the microspheres increased with increasing Eudragit RL/RS ratio and stirring rate during the preparation, and with decreasing the polymer concentration of internal phase and microsphere size. It was found that a linear relationship existed between the microsphere size and the time of 50% drug release. The drug release rate increased with increasing nifedipine content from 4.2 to 16.7% and was more rapid than the dissolution rate of pure nifedipine particles. However, the release rate of the microspheres with 26.6% drug content decreased significantly and was slower than the dissolution rate of pure drug particles. This was attributed mainly to the nifedipine dispersion state in the microspheres as confirmed by the differential thermal analysis and X ray diffraction study, which showed that nifedipine was present in an amorphous or molecular state in the microspheres with 4.2, 9.4 and 16.7% drug, whereas partly in the crystalline state in the microspheres with 26.6% drug. The amounts released for less than 70% nifedipine can be fitted to Higuchi square root of time model, independent of polymer ratio, drug content and microsphere size.

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.