ABSTRACT
Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure. All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death. The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues. These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor. Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH. In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of "lung distension";(4)research into monomers of traditional Chinese medicine; and(5)research into new targets.
ABSTRACT
@#Drug Administration Law revised in 2019 proposed for the first time conditional marketing authorization at the legal level, marking the formal implementation of the conditional marketing authorization in China. This paper compares the regulations and technical requirements of conditional marketing authorization drugs in China with those in Europe and the United States, in an attempt to learn from the experience of chemistry, manufacture and control review of these drugs in Europe and the United States, and to discuss the pharmaceutical technical requirements of conditional marketing authorization drugs in China.
ABSTRACT
Respiratory syncytial virus (RSV) is an RNA virus, which belongs to the paramyxoviridae family, and is transmitted by air droplets and close contact and the main pathogen causing acute lower respiratory tract infection in infants, the elderly and immunocompromised individuals.Although there have been studies on the prevention and treatment of RSV drugs and RSV infection in patients, many medical demands have not been met.And there is no specific antiviral therapy.The only two drugs approved to be applied in RSV prevention and treatment are perizol and ribavirin.However, the former must be used prophylactically, and primarily in high-risk children, while the latter is less effective, and some children even suffer from airway spasm.Therefore, it is urgent to propose new methods for prevention and treatment of RSV.In recent years, traditional Chinese medicine(TCM) has shown a good anti-RSV effect, with a fewer side effects, less resistance to drugs and broad-spectrum antiviral advantage.There are also newly developed biological and chemical anti-RSV drugs.Some new drugs have shown a good efficacy, with an extended half-life and reduced costs, such as fusion inhibitors, monoclonal antibodies.This paper reviews the research progress of anti-RSV drugs in the aspects of TCM, biological drug and chemical drugs, laying a foundation for the development of new anti-RSV drugs and the formulation of new therapeutic strategies.
ABSTRACT
Polymorphism of chemical drugs has become a hot topic in pharmaceutical research at home and abroad. In this review, the phenomena, causes and significance of polymorphism were introduced briefly. The international drug development process and characteristics of the polymorphic drug development in our country were analyzed. Finally, the present situation and development in China was summarized from four aspects including the basic theory, technical methods, intellectual property rights and supervision. This paper can provide a reference for correct understanding the research level of polymorphic drugs in China and clarifying the direction of polymorphic drug research.
ABSTRACT
The China Food and Drug Administration (CFDA) modulated the Drug Registration Regulation at 2016.In this article,the registration classification of chemical drug was analyzed,and the definition,cormotation and technical standard of new drugs and generic drugs were compared.Compared with the 2007 version of regulations,obvious changes have happened,the scope of new drugs has been narrowed,and the definition is more strict and accurate,the scope of generic drugs has been expanded.The new regulation keeps the same evaluation standards with the ICH,FDA and EMA.Regulatory changes have a profound impact on the medical research and development:promoting the reformulation of domestic pharmaceutical market,encouraging R&D and innovation in enterprises and accelerating the pace towards the international market.
ABSTRACT
Objective:To evaluate the capacity and level of melting point determination of chemical drugs in the laboratories par-ticipating in the proficiency testing. Methods:Two test samples were prepared, and the labs volunteered to participate in the proficien-cy testing program ( PTP) . The melting point determination was performed according to the general principle 0612 in part four of Chi-nese Pharmacopoeia (2015 edition), and the results were analyzed by robust statistics and the determination proficiency of the laborato-ries were evaluated by Z-score. Results:The analysis showed that two test samples were homogeneous and stable, which met the re-quirements of the PTP. Totally 31 laboratories had satisfactory results, which accounted for 83. 8%. Conclusion:The majority of the participant laboratories can accurately determine the melting points of test samples, and the information is very helpful to the next profi-ciency testing program.
ABSTRACT
Wnt signals widely exist in live creatures,involved in many physical or pathological processes,including the cell prolif-eration, differentiation and apoptosis. Recent studies show that Wnt/β-catenin signaling pathway may play an important regula-tory role in the protective effects of neurovascular unit in ische-mic stroke. Some chemicals,such as sulindac and estradiol,and some compound traditional Chinese medicine which contains gly-coside( e. g. rhodiola rosea ) , volatile oil ( e. g. turmeric ) and compound prescription ( e. g. Dan Long Xing Nao Fang ) can protect the neurovascular unit by regulating the pathway. This aims to review the research progress of the protective effects of Wnt/β-catenin signaling pathway on the neurovascular unit in is-chemic stroke,with combination of chemicals and traditional Chi-nese medicine which can protect the neurovascular unit via Wnt/β-catenin signaling pathway. It aims to provide the methodology basis for elucidating the mechanism of drugs,and also provide a new idea for researching the new drug which can reduce the dis-ability rate caused by sequela of stroke.
ABSTRACT
Ion chromatography(IC)can make up the deficiency of LC or GC for the analysis of ionic drugs because of the unique separation mechanism,so IC is more and more widely applied in the field of drug analysis. In the paper,the application of IC is reviewed in the quality control of chemical drugs.
ABSTRACT
Objective: To estabilsh a rapid and accurate method for the determination of 17 anti-inflammatory and analgesic chemicals (paracetamol, aspirin, phenacetin, chlorpheniramine maleate, rofecoxib, piroxicam, lornoxicam, meloxicam, prednisone acetate, sulindac, naproxen, dexamethasone acetate, phenylbutazone, oxaprozin, celecoxib, diclofenac sodium, and indomethacin) which were illegally added into the Chinese patent medicines (CPM) and the health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) and 0.1% formic acid water (B) as the mobile phase by gradient elution (0-4 min, 40% A; 4-5 min, 40%-50% A; 5-6 min, 50%-60% A; 6-12 min, 60%-80% A; 12-13 min, 80% A; 13-14 min, 80%-40% A) at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and a MRM mode were used to separately and quantitatively determinate the 17 anti-inflammation and analgesia chemicals. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 17 chemicals by comparison with those of reference substances. The obtained peak areas were used to determinate the accurate content of chemicals in commonly used drugs in clinic. Results: A good resolution of the 17 chemicals, including paracetamol, aspirin, phenacetin, chlorpheniramine maleate, rofecoxib, piroxicam, lornoxicam, meloxicam, prednisone acetate, sulindac, naproxen, dexamethasone acetate, phenylbutazone, oxaprozin, celecoxib, diclofenac sodium, and indomethacin was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.3-5.0 and 0.9-15.0 ng/g. The standard addition recoveries were in the range of 90.5%-113.8%. The six components in samples (paracetamol, prednisone acetate, diclofenac sodium, indometacin, chlorpheniramine maleate, and naproxen) were detected. Conclusion: The method is simple, accurate, and has high sensitivity, which can be used for the qualitative and quantitative determination of illegally added chemicals in CPM and health foods.
ABSTRACT
Objective: To establish a rapid and accurate method for the determination of 15 chemical drugs which were illegally added into the slimming Chinese patent medicines (CPM) and health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) -0.1% formic acid water (B) as mobile phase by gradient elution (0-3 min, 33%-45% A; 3-5 min, 45%-55% A; 5-7 min, 55%-70% A; 7-9 min, 70%-80% A; 9-10 min, 80%-90% A; 10-11 min, 90%-33% A; 11-13 min, 33% A at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and an MRM mode were used to separate and quantitatively determine 15 chemical drugs. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 15 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate contents of chemical drugs in CPM and the health foods. Results: A good resolution of 15 kinds of chemical drugs, including terbutaline hydrochloride, ephedrine hydrochloride, theophylline, caffeine, doxofylline, clenbuterol hydrochloride, tulobuterol hydrochloride, bambuterol hydrochloride, fenfluramine hydrochloride, furosemide, indapamide, phenolphthalein, sibutramine hydrochloride, N-demethylated sibutramine hydrochloride, and hydrochloric acid N,N-dinor sibutraminel, was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.1-5.0 ng/g and 0.3-15.0 ng/g. The standard addition recoveries were in the range of 91.8%-110.8%. In the 86 batches of samples (including capsules, granules, and other different matrix types) were detected in the 74 batches of added chemicals, the positive rate was 86.0%. Sibutramine hydrochloride (39 batches), furosemide (20 batches), phenolphthalein (23 batches), theophylline (1 batch), and caffeine (15 batches) were checked out in the samples, 22 batches of which two kinds were checked out, one batch of which three kinds were checked out. By contrast, the products which were not clearly marked manufacturer illegally added more seriously. Conclusion: The method is simple, accurate, and highly sensitive, which can be used for the determination of illegally added chemical drugs in slimming CPM and health foods.
ABSTRACT
Objective: To establish an accurate method for the determination of nine chemical drugs (phentolamine mesylate, methyltestosterone, stanozolol, danazol, tadalafil, sildenafil citrate, aildenafil, vardenafil, and thioaildenafil) which were illegally added into the antifatigue health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH-C18 (100 mm × 2.1 mm, 1.7 μm) column with 0.1% formic acid methanol (A) and 0.1% formic acid water (B) as the mobile phase by gradient elution (0-5 min, 50% A; 5-7 min, 50%-90% A; 7-9 min, 90%-100% A; 9-10 min, 100%-50% A) at a flow rate of 0.2 mL/min. The injection volume was 5 μL. The column temperature was 40 ℃. The positive-ion (ESI+) source and MRM mode were used to separate and quantitatively determine the chemicals. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the nine kinds of drugs by comparing with those of reference substances. The obtained peak areas were used to determine the accurate content of the nine chemicals in the antifatigue health foods. Results: A good resolution of the nine kinds of chemical drugs, including phentolamine mesylate, methyltestosterone, stanozolol, danazol, tadalafil, sildenafil citrate, aildenafil, vardenafil, and thioaildenafil, was obtained under this UPLC and MS/MS conditions. The limits of detection (LOD) and quantification (LOQ) were in the ranges of 0.1-0.3 ng/g and 0.3-0.9 ng/g. The standard addition recoveries were in the range of 88.4%-116.3%. There were 68 batches of antifatigue health foods, among which 41 batches were added with the chemicals with positive rate of 60.3%. The sildenafil citrate, tadalafil, aildenafil, and hioaildenafil were detected in samples. Conclusion: The method is simple, accurate, and has high sensitivity, which can be used for the qualitative and quantitative determination of illegally added chemical drugs in the antifatigue health foods.
ABSTRACT
Objective To observe the effect of integrated therapy of Chinese medicine and chemical drugs on adverse reaction and curative effect of initial treatment of secondary pulmonary tuberculosis. Methods Totally 1404 patients with secondary pulmonary tuberculosis and TCM lung consumption diagnostic criteria (syndrome of lung yin deficiency, qi-yin deficiency, yin-deficiency caused excessive fire) were chosen for single blind, randomized, controlled, multicenter clinical trials. Trial group was given 2HRZE/4HR, 1 time/day with Chinese medicine 2 or 3 times/day, and control group was given 2HRZE/4HR only for six months. The adverse reactions and clinical symptoms were observed to evaluate clinical efficacy and safety. Results In terms of reducing liver damage and other adverse reactions, the ratio of trial group had statistical difference with that of control group (P<0.001). In symptom scores of lung yin deficiency syndrome treated for 2, 4, 6 months, yin-deficiency caused excessive fire syndrome treated for 6 months, qi-yin deficiency syndrome treated for 4, 6 months, the differences between the two groups were significant (P<0.001). TCM syndrome curative effect between the two groups was statistical different (P<0.001). Safety evaluation result between the two groups was statistical different by tratified analysis (P<0.001). Conclusion Integrated therapy of Chinese medicine and chemical drugs can improve the symptoms and reduce adverse reactions caused by chemical drugs. It can enhance the curative effect and safety.
ABSTRACT
Objective To discuss the effects and mechanisms of tetramethylpyrazine(TMP)on learning and memory abilities of Alzheimer's disease(AD)mice.Methods The animal models of AD were induced by aluminium trichloride(AlCl3)intragasticly for forty days.Then,TMP was intragastricly administered for twenty days.The escape latency of the mice in water maze test was recorded;and AChE and SOD activities and MDA levels in the brain were detected by chemical eoiorimetrie method.The expressions of At3 and NF-κB in the cerebral cortex were measured by immunohistochemistry method.Results 1)TMP has markedly decreased escape latency in AlCl3 induced AD mice(P＜0.05).2)In the brain of AlCl3 induced AD mice,TMP reduced AChE activity 19%[(1.37±0.13)U·mgpro-1vs(1.69±0.27)U·mgprot-1,P=0.016],decreased MDA levels 34% [(43.63 4-13.27)nmol·mgprot-1 vs(28.59±8.52)nmol·mgprot-1,P=0.023]and increased SODD activity 39%[(55.81±10.25)U·mgprot-1 vs(40.04±13.06)U·mgprot-1,P=0.026],respectively.These resuits showed significant difference with model mice group(P＜0.05).3)TMP also decreased AB and NF-κB expressions in the cerebral cortex of AD mice models(P＜0.05).Conclusion In AlCl3 induced AD mice,TMP can remarkably enhance the learning and memory abilities,presumably in relation to raise the activity of SOD,reduce the activity of AChE,the levels of MDA and the expressions of AB and NF-κB in the brain.
ABSTRACT
Drugs or toxic chemicals related anemia was mainly mediated by suppression of hematopoietical stem cells and/or precursors,then caused hematopoietical failure;or shortened the survival of red cells.Carefully gathering information of history and physical examination was vital,and experiment examinations could also make definitely classifications of anemia.Detachment,excretion and neutralization of these drugs or toxic chemicals should be conducted in time,support care and anti symptomatic therapy would be very useful.Long-term following-up for some patients was necessary to evaluate the transformation of disease.
ABSTRACT
OBJECTIVE:To improve package inserts of chemical drugs so as to promote safe,rational and effective use of chemical drugs.METHODS:A total of 558 package inserts of different chemical drugs commonly used in the clinic were collected from our hospital and other local hospitals and analyzed statistically based on the regulations stipulated by the "Norms of Package inserts of Drugs(trial)".RESULTS:Some important items such as pharmaco-toxicology,usage and dosage,pharmacokinetics etc in the package inserts of chemical drugs failed to meet the state standards,but the package inserts of the imported chemical drugs superior to those of the domestic ones,those of the injections superior to those of oral preparations,and those of oral preparations superior to those of external preparations.CONCLUSION:The package inserts of chemical drugs are far from perfect,which thus remain to be improved further.