Showing papers in "Chinese New Drugs Journal in 2004"

The efficacy of Cordyceps militaris capsules in treatment of chronic bronchitis in comparison with Jinshuibao capsules

Abstract: Objective: To evaluate the efficacy and safety of Cordyceps militaris capsules in treatment of chronic bronchitis. Methods:The multi-centers,randomized,single blind,and positive controlled study was conducted in 425 patients with chronic bronchitis. They were divided to receive Cordyceps militaris capsules in a dose of 1g tid for 2 months ( n = 315) or Jinshuibao capsule in a dose of 1g tid for 2 months ( n = 110). Results:The symptom of cough,sputum,and wheeze as well as lung function, chest X ray syndrome and comprehensive efficacy in the active group were significantly improved compared with control group (P 0.01). No significant difference in blood routine examination, liver and renal functions, ECG and others between 2 groups were observed (P0. 1). Conclusion : Cordyceps militaris capsules are effective in treatment of chronic bronchitis.

A phase I clinical trial for recombinant human endostatin

Abstract: Objective:To determine the maximum tolerated dose (MTD) and the pharmacoki-netics of the endostatin (rh-endostatin, YH-16) injection in human. Methods: 12 healthy volunteers were equally divided into 4 groups. Each group was intravenously administrated with a single dose of YH-16 infusion at 30,60,120 and 210mg·m-2,respectively. 10 patients with advanced solid tumors were categorized into 3 groups (4,3 and 3 patients per group). Each group was intravenously given with a dose of YH-16 infusion at 7.5,15 and 30mg·m-2 once daily for 28 days, respectively. The YH-16 concentration in serum sampes from all subjects was analyzed by ELISA,so as to determine the pharmacokinetic profile. Results:The dose limiting toxicities (DLT) were measured as varieties of car-diac adverse reactions, including sinus arrhythmia, supraventricular tachycardia, ventricular premature beat and T wave changes shown in electrocardiogram. The other mild adverse events were found to be fever,rash, minor dizziness, headache, fatigue, palpitation, chest discomfort and diarrhea. One patient with malignant melanoma had a minor response and 5 patients showed stable disease.The pharmacokinetic disposition was almost linear in healthy volunteers. However,the individual difference on concentration vs. time was observed in patients with advanced solid tumors. Conclusion:The YH-16 was clini-cally tolerated well.The MTD was 120mg·m-2 in healthy volunteers with a single dose, and 15mg· m-2 in the tumor patients with a daily dose for 28 days. The efficacy of anti-tumor with YH-16 was evident.The clinical dosage of 12mg·m-2 daily for 28 days in phase Ⅱ study is recommended.

Synthesis of chidamide,a new histone deacetylase (HDAC) inhibitor

Abstract: Objective:To synthesize chidamide {N-(2-amino-5-fluorophenyl)-4-[N-(pyridn-3ylacryloyl) aminomethyl ] benzamide}, a new histone deacetylase (HDAC) inhibitor. Methods: 3-Pyridineacrylic acid was prepared from 3-pyridine carboxaldehyde by Knoevenagel reaction, which was converted to the title compound by 2 steps of acetylation in the presence of N, N'-carbonyl diimida-zole. Results: Chidamide was synthesized in a total yield of 29% . Conclusion: A gentle and easily con-trolled process for synthesis of chidamide is worked out.

The adverse drug reactions of antifungal agents

Abstract: Nowadays hypoimmunity cases were increasing because many clinical diseases could induce it and the incidence of fungal infections was greatly increased. Accordingly, clinical use of anti-fungal agents was wider and wider. Most antifungal agents didn't have specific selectivity in treatment of fungal infections. While fungi were killed, the host cells were also intoxicated. Therefore, ADRs of these agents was the vital factor to limit them uses. In this paper,the adverse reactions of antifungal a-gents commonly used were reviewed.

Studies on the absorption and excretion of crocin-1 in rats

Abstract: Objective: To study the absorption and excretion of crocin-1 post dosing in rats. Methods:The intestinal absorption was investigated by in situ perfusion in rats. The various intestinal segments were incubated in vitro with crocin-1 for 2 and 4 hours at constant temperature. The absorption and excretion of crocin-1 were also studied in vivo by pouring of crocin-1 into stomach. The absorption and excretion rate of crocin-1 were determined by HPLC. Results:Elimination rate of crocin-1 in various intestinal segments after in situ perfusion for 4 hours was as follows:duodenum 10.1% jejunum 9.55% ,ileum 9.15% ,colon 12.24% .Degradation rate of crocin-1 after the incubation in blank refluxing solution on various intestinal segments for 4 hours was as follows:duodenum 9.85% ,jejunum 10.85% ,ileum 11.49% .colon 12. 64%. The excretion rate of crocin-1 in the stool and the intestinal tract was 79.9% in rats after the dosing at 50mg·kg-1 into stomach for 24 hours. No crocin-1 was found in blood and urine of the rats. Conclusion:The parent crocin-1 is not able to be absorbed from the intestinal tract.

Synthesis of 3-benzylthiochromanones and their in vitro antifungal activity

Abstract: Objective:To synthesize 3-benzylthiochromanoes and measure their in vitro antifun-gal activity. Methods:Substituted thiophenols were used as starting material, the target compound was synthesized through several steps and their in vitro antifungal activity was studied. Results: 6 new compounds were synthesized and IR, 1H-NMR and elemental analysis were used to elucidate their chemical structure. Conclusions: The 3-benylthiochromanones synthesized have in vitro antifungal activity to most fungal strains tested.

Current status of fourth-generation quinolone

Abstract: Quinolone is known as broad antibacterial spectrum,high potency,no crossing drugresistance with other antibacterial drugs,and easy and low cost to administer.The article introduces thehistory,clinical features and rationale,pharmacodynamics and pharmacokinetics of fourth generationquinolone.

Molecular mechanisms for drug resistance of Candida albicans

Abstract: The emergence of fluconazole-resistant Candida albicans strains is a significant problem after long-term treatment. Multiple molecular mechanisms contribute to the development of resistance in Candida albicans .including mutations or overexpression of the drug target enzyme in sterol biosynthesis, such as sterol 14α-demethylase,alternations of intracellular drug concentration by multidrug resistance pumps and the formation of biofilm in Candide albicans.

Synthesis of 3-pyridineacetic acid hydrochloride

Abstract: Objective:To synthesize 3-pyridineacetic acid hydrochloride Methods:Starting from 3-acetylpyridine prepared by esterfication and condensation of nicotic acid, 3-pyridineacetic acid hydrochloride was synthesized from the intermediate 3-pyridylthioacetmorpholide via hydrolysis and acidification Results and Conclusion:The process is more moderate and simpler with overall yield of 510%

Recent advances in research of garlic's chemical constituents and theirs pharmacological effects

Abstract: Garlic is a bulbous root of Allium sativum with antitumor,antimicrobial,and hy-polipidemic effects. Its main chemical constituents are composed of organosulfur compounds and steroid saponins. The organosulur compounds can be subdivided into lipid - soluble and water - soluble compounds . The former possesses a stronger antitumor effect while the latter have a stronger hypolipidemic effect. The water-soluble component has a very minor toxicity and worth to be further studied.

Efficacy of Cordyceps militaris capsules in treatment of chronic bronchitis

Abstract: Objective:To observe the efficacy of Cordyceps militaris capsules in treatment of chronic bronchitis. Methods: The phase Ⅲ clinical trial was conducted in 510 patients with chronic bronchitis. The symptoms of cough,sputum, wheeze and wheezing rale,as well as lung function,chest X ray examination, and others were recorded before and after treatment with Cordyceps militaris capsules. Data obtained were statistically analyzed and the safety of the drug was also observed. Results: The symptom in patients with chronic bronchitis was significantly improved after treatment with Cordyceps militaris capsules (P 0. 05) with an effective rate of 88. 04% . Conclusion: Cordyceps militaris capsules is an effective agent for treatment of chronic bronchitis.

Structure-activity relationship of pentacyclic triterpenes

Abstract: Pentacyclic triterpenes as aglycones of saponins have a wide distribution in plants,many of which have been used in empirical anti-inflammatory therapies.Recently,researches demon-strated that some triterpenoids have favorably biological activities in inhibition of tumor cell prolifera-tion,induction of apoptosis,and anti-viral therapy of AIDS.This article is reviewing the structure-ac-tivity relationship of pentacyclic triterpenes.

Improvement of the dissolution rate of Ginkgo biloba tablets by using solid dispersion methods

Abstract: Objective:To improve the dissolution rate of extraction of Ginkgo biloba (EGb) tablets. Methods:Two carriers (PEG 6000 and PVPK17) and solid dispersions in different ratio were prepared by solvent-melting or spray-drying technique. The dissolution characteristics of solid dispersion, mechanical mixtures,EGb and Ginkgo biloba tablets obtained from market were compared. The EGb-PEG 6000 solid dispersion were studied by differential scanning calorimetry. Results: EGb-PEG 6000 and EGb-PVPK17 solid dispersion of different ratio can be prepared by solvent-melting or spray-drying technique. The dissolution rate of EGb-PEG 6000(1: 2) were significantly improved and the im-provement was superior to EGb-PVPK17. Conclusion: The clissolution rate of EGb tablets can be effec-tively improved by preparation of EGb-PEG 6000 (1:2) solid dispersion.

Phase I clinical trial of sodium glycididazole (CMNa) in cancer patients

Abstract: Objective:To establish the maximum tolerance dose (MTD) of CMNa and to observe the adverse drug reactions of CMNa. Methods: 32 patients with cancer were divided to receive 3 times weekly intravenous injection of 6 different doses (400-900mg·m-2) of CMNa for 3 or 6 consecutive weeks and routine radiotherapy given by fractional delivery were also given simultaneously. The urine and serum CMNa concentrations were determined by HPLC. Results:The maximum tolerance dose for CMNa was 900mg · m-2 . The main adverse drug reactions observed were mild gastrointestinal duct reactions including nausea,vomiting,constipation (4/33),mild and reversible SALT and bilirubin rise,and changes in cardiac function and ECG of different degree including ST-T depression, arrhythmias and palpitation were occurred when larger doses were given. No nervous system adverse drug reactions were observed. Conclusion: CMNa used as a radiosensitizer in 3 times weekly dose of 800mg·m-2 given by intravenous injection for 6 consecutive weeks is tolerable and this regimen is recommended to be used in phase Ⅱ clinical trial.

The effects of tetrahydroxylstilbene on learning and memory ability and NMDA-receptor binding to [~3H]MK801 in forebrain of ischemia-reperfusion gerbils

Abstract: Objective:To study the effects of tetrahydroxylstilbene on learning and memory a-bility and NMDA (N-methyl-D-aspartate) receptor to [3H]MK801 in brain of ischemia-reperfusion gerbils. Methods:The bilateral carotid ateries of gerbils were occluded for 10min with micro-aneurysm clips and then reperfused. 7d later, the alternation in learning and memory ability was evaluated by MWM (Morris water maze). NMDA receptor binding force of forebrain tissue was assayed after sacrifice of gerbils. Results: Result of MWM evaluation showed that the swimming time and distance of model group were significantly prolonged compared with sham-operation group, while those of tetrahydroxylstilbene treated group were shortened. The assay of NMDA receptor binding test indicated that the receptor binding force of model group was higher than that of sham-operation group. Tetrahydroxylstilbene treatment can markedly reduce the binding force. Conclusion: Tetrahydroxylstilbene can ameliorate the learning and memory dysfunction of ischemia-reperfusion gerbil model and reduce NMDA receptor-binding force,so tetrahydroxylstilbene may have brain protective effect.

Synthesis of chiglitazar, a new insulin sensitizer

Abstract: Objective: To synthesize chiglitazar, (2S)-2-[2-(4-fluorobenzoyl) phenylamine]-3-[4-(2-carbazol-9-yl-ethoxy)-phenyl]-propionic acid,a new insulin sensitizer. Methods:Chiglitazar was synthesized from 2-(4-fluoro)benzoylcyclohexanone, L-tyrosine methyl ester and 1,2-dibromoethane via 3 steps. Results: A total yield of 10. 8% was obtained. Conclusion: A short and easily controlled process for synthesis of chiglitazar is established.

Synthesis of derivatives of N-alkyl-5-hydroxy-1H-indole-3-carboxylic ester hydrochloride

Abstract: Objective: To synthesize some derivatives of N-alkyl-5-hydroxy-lH-indole-3-car-boxylic ester hydrochloride using arbidol as leading compound. Methods: Using 4-chloroethyl acetoac-tate as starting material, the target compounds were synthesized through 5 unite reactions, including sulfurizing,amination,Nenitzescu reaction, Mannich reaction and salt formation. The end up of reaction was determined by TLC. Results: The chemical structure of these target compounds were confirmed by IR,1H-NMR and MS. Conclusion: 9 unreported derivatives of N-alkyl-5-hydroxy-1H-in-dole-3-carboxylic ester hydrochloride were synthesized by this way.

Clinical application of flurbiprofen axetil injection

Abstract: Flurbiprofen axetil injection is a lipid microspheres formulation that is used to relieve postoperative and cancinous pain. The formuation may provide clinical benefits by exhibiting reduced adverse reactions compared to the oral formulation. The pharmacological benefits and clinical advantages were reviewed.

Formulation of nisoldipine sustained release tablets

Abstract: Objective: To optimize the nisoldipine sustained release tablets formulation. Methods: The formula and manufacturing process of nisoldipine sustained release tablets were optimized by selecting appropriate sustained release agents and excipients. Results: The sustained release tablet showed a sustained release of the active ingredient for over 12 hours when hydroxypropyl methylcellu lose was used as a sustained release agent and hydroxypropyl cellulose as a binder. Conclusion: The manufacturing process of nisoldipine sustained release formula was easily manipulated.

The efficacy and safety of recombinant human epidermal growth factor in 4 types of wounds

Abstract: Objective: To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in 4 types of wounds. Methods: 134 patients were assigned to one of 4 daily treatment groups based on their wounds:superficial burn on faces (30 patients) ,deep partial-thickness burn on faces (30 patients),partial-thickness donor site on thighs (30 patients) ,or chronic foot sepsis due to diabetes (44 patients). In the first 3 groups,the wounds on both same area and degree were applied either with rhEGF as a treatment or with antibiotics as a control. The last group was further randomized to receive either rhEGF or antibiotics alone in a ratio of 1:1. In all treatment groups,rhEGF was reconstituted with 20mL of saline solution prior to its application to the wounded area. The gauze was used as effective vehicles for rhEGF or antibiotics to coat on the wounded area. The medicated gauzes were changed daily till the wounds healed. Results: The wounds healed sooner and better by rhEGF than by antibiotics. No adverse effects were reported. Conclusions: rhEGF can promote the healing rate and healing quality to the wounds. The safety of rhEGF is evident.

The efficacy and safety of lornoxicam in treatment of rheumatoid arthritis and osteoarthritis

Abstract: Objective:To study the efficacy and safety of lornoxicam in treatment of rheumatoid arthritis and osteoarthritis Methods: The randomized and double blind study was conducted in 34 patients with rheumatoid arthritis and 48 patients with osteoarthritisThey were randomly divided to re-ceive lornoxicam 8mg/week for 3 weeks or placebo for 3 weeks Results: After treatment, the mean Huskinssion's VAS was reduced by 31 80 for active group and 8 20 for control group and the incidence of ADRs was 731% for active group and 4 87% for control group Conclusion:Lornoxicam is effective in treatment of rheumatoid arthritis and osteoarthritis with mild adverse reactions

The influence of astragalosides on articular cartilage and synovium in rabbit in vitro

Abstract: Objective:To study the effect of astragalosides(AST)on joint damage in vitro. Methods: The levels of 35S incorporation in articular cartilage and the levels of 3H-TdR incorporation in synovial fibroblast from rabbits were detected. Results: In vitro treatment of AST(0.8-3.2mg·L-1) could enhance the decreased proteoglycan synthesis of articular cartilage induced by rhIL-1(30 U·mL-1)or Fe2+ -H2O2(each 10μmol·L-1)system as well as suppress increased proliferative responses of synovial fibroblasts induced by low Fe2+-H2O2 system(each 20μmol·L-1). Further study showed that AST could scavenge OH' directly. Conclusion: AST could protect against joint damage induced by Fe2+ -H2O2 system and rhIL-1 ,which might be related to the effect of AST on scavenging OH'.

The effects of scutellarein on platelet cytosolic free calcium concentration,platelet aggregation rate,and heart remodeling in rats

Abstract: Objective:To study the effects of scutellarein on platlet cytosolic free calcium concentration, platelet aggregation rate and heart remodeling in spontaneously hypertensive rats (SHR). Methods:24 SHRs aged 10 months with left ventricular hypertrophy(LVH) were randomly divided to receive scutellarein, fosinopril, enapril or 0.9% NaCl solution for 8 weeks and the systolic blood pres-sure(SBP), heart rate (HR), left ventricular hypertrophic index (LVW/BW), ultramicrostructure of myocardial cell, platelet cytosolic free calcium concentration (PCFCC) and platelet aggregation were observed. Results: SBP,LVW/BW,PCFCC and degree of platelet aggregation in SHR group were respectively higher than that in Wistar Kyoto rates group. Ultramicrostructural changes including myocardial hypertrophy, sarcoplasmic reticulum expension and mitochondrion hyperplasia occurred in SHR group. The PCFCC and degree of platelet aggregation were positively correlated to LVW/BW in SHR with LVH. The significant decrease in LVW/BW,PCFCC,and degree of platelet aggregation as well as amelioration of ultramicrostructure myocardial hypertrophy were achieved in scutellarein,fosinopril and enalpril groups compared with control. Fosinopril and enalapril can also significantly decrease the SBP of SHR.Conclusion:Abnormal metabolism of PCFCC and changes in platelet function play an important role in heart remodeling of SHR. Scutellarein,fosinopril,and enalapril can significantly decrease the PCFCC and rate of platelet aggregation,therefore can improve heart remodeling in SHR.

Investigation on the corneal permeability of enoxacin in vitro

Abstract: Objective:To explore the corneal permeability of enoxacin (ENX) in vitro. Methods : The permeable characteristics of ENX across the cornea of an isolated rabbit were studied in vitro using a variety of osmotic enhancers. Results: 1% poloxamer (F68) and 2% HP-β-CD showed a significant increment as much as 1. 65 and 2.05 times in the apparent permeability of ENX, respectively, compared with the ones in the control (P0.01). However,0.05% Azone and 0.5% EDTA did not improve the apparent permeability of ENX. The enhancers insignificantly changed the lag time pertinent to the corneal permeability.1% poloxamer (F68) and 0.05% Azone were irritable to eye tissues. Conclusion:2% HP-β-CD serves the corneal apparent permeability of ENX better.

Clinical effect of ornidazole injection in treatment of anaerobic infections in gynecology

Abstract: Objective: To study the safety and efficacy of ornidazole injection in treatment of anaerobic infections in gynecology. Methods: 94 female patients with anaerobic infection were randomly divided to receive twice daily infusion of ornidazole injection 500mg plus normal saline or twice daily infusion of metornidazole injection 500mg plus normal saline for 5d. Results:The total effective rate,bacterial clearance, and incidence of ADR were 72. 3% , 85. 0% , and 6.4% respectively for the active group and 66.0% ,81.0% ,and 8.5% respectively for the control group. Conclusion:Orindazole injection is effective in treatment of anaerobic infections in gynecology.

Pharmacokinetics of esomeprazole

Abstract: Esomeprazole,a S-isomer of omeprazole,is the first isomer-PPI developed. It has an advantage in metabolism and resulted in a higher bioavailability and consistent pharmacokinetics in comparison with omeprazole. The acid control ability of esomeprazole is superior to those of omeprazole and all other PPIs.

Sulfobutyl ether-β-cyclodextrin--a new excipient and its applications in pharmaceutics

Abstract: In order to promote its further research and application, the properties and safety of sulfobutyl ether-β-cyclodextrin and its envelope characteristics and uses in pharmaceutics were reviewed in this paper.

Synthesis of indomethacin derivatives and their anti-inflammatory activities

Abstract: Objective:To search for new NSAIDs with higher efficacy and lower toxicity Methods : Indomethacin derivatives were prepared from halohydrocarbons, nitrobenzyl alcohol and netroben zychloride by reactions of condensation and esterfication Results and Conclusion: 6 new compounds have been synthesized,among them compound 3a,3c and 5b had an anti-inflammatory activity comparable to or higher than indornethathcin

The relationship between hypoxemia and SARS complicated liver injury and the efficacy of reduced glutathione in treatment of the disease

Abstract: Objective:To observe the efficacy of reduced glutathione (TAD) on SARS complicated liver injury. Methods: 37 patients with SARS complicated liver injury were treated with TAD 600mg once daily given by infusion after dissolved in 5% glucose injection for 2 weeks and their hepatic functions (ALT,AST,GGT) were determined before and after treatment. Results:The hepatic functions were significantly improved after treatment and the effective rate of reduced glutathione in this study was 81.1% ,no adverse drug reactions were observed.Conclusion:TAD show satisfactory therapeutic effect in treatment of SARS complicated liver injury.

Pharmacokinetics of torasemide tablets in healthy volunteers

Abstract: Objective:To assess pharmacokinetics (PK) profiles of torasemide tablets in Chinese healthy volunteers Methods: A single oral dose, three-cycle,crossover,open Latin square study was performed in 9 healthy volunteers The volunteers were randomized to receive torasemide at 5,10 and 20mg, respectively The plasma torasemide concentration was determined by HPLC Results: Torasemide was rapidly absorbed when given orally Tmax of 5,10,20mg torasemide was all about 1hour post administration, and the apparent volume of distribution ( Vd) 17L The ratio of Cmax of 5, 10,20 mg torasemide was 1:2 3:4 6,and the area under the plasma torasemide concentration versus time curve (AUC0-14) was 1:20:45 and (AUC0-∞) 1:20:44 (r=0999)t1/2 of 5,10,20mgtorasemide was (377±125), (360±068), (374±070)h,respectively The difference in the total body clearance (Cl) at the three dosages was [(564±148), (563±103), (516±128)mL·min-1 respectively] not of statistically significance (P 0 05) Conclusion: The PK profiles of torasemide in Chinese population show the linear relation of the log of the concentration versus time for a first-order reaction that is similar with the ones in Western population