This study discussed problems in consistency assessment of generic drugs and analyzed effect of polymorphs on drug quality and its influence on consistency of curative efficiency.Relationship between evaluation method of polymorphs and curative efficiency was investigated.It showed that establishment of curative efficiency related evaluation indicators was necessary and improvment of techniques was important.Drug quality criteria should be added with requirement of curative efficiency control.Related information based on polymorphs could be provided for technical research in consistency assessment.
Tacrolimus is a novel immunosuppressant used in the treatment of a variety of autoimmune diseases.More and more studies have shown that tacrolimus has a certain therapeutic effect on myasthenia gravis (MG).This article reviews the mechanism,clinical researches,adverse reactions,dosage and clinical evaluation of tacrolimus in the treatment of MG.
Objective To investigate the influence of isoquercitrin on the inflammatory factors in LPS-induced RAW264.7 cells. Methods MTT method was used to detect inhibition ratio of RAW264.7 cells induced by isoquercitrin.The level of TNF-α in culture medium was measured by ELISA.Nitric oxide (NO) was detected by Nitrate Assay Kit.Western blotting was used to investigate the influence on the productions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Results The half inhibitory concentration (IC50) of isoquercitrin was 65.73 μmol·L-1.LPS had no inhibitory effect on the cells.Compared with LPS group,the level of TNF-α was decreased to 74.80% and 60.57% in isoquercitrin (20,10 μmol·L-1) groups in a dose-dependent manner.The results measured by Nitrate Assay Kit revealed that isoquercitrin (20,10 μmol·L-1) could suppress production of NO,the level of NO decreased to 79.34% and 68.81%(P<0.05). The Western blotting results showed that isoquercitrin (20,15,10 μmol·L-1) inhibited the productions of iNOS and COX-2 (P<0.05). Conclusion Isoquercitrin has anti-inflammatory effects by inhibiting the productions of TNF-α,NO,iNOS and COX-2,and the most effective dose for the inhibition is 10 μmol·L-1.
Objective To explore the relationship between vitamin D and depression and the effects of chronic unpredictable mild stress (CUMS) plus sertraline on vitamin D metabolism in rat brain. Methods Male SD rats were randomly divided into normal control group,normal control + sertraline group,CUMS group and CUMS+sertraline group.CUMS was used to build the animal model of depression.After chronic exposure to CUMS or sertraline (8 mg·kg-1·d-1) for 6 weeks,behavioral response (sucrose preference test) and vitamin D metabolism in the prefrontal cortex were analyzed. Results Compared with normal control group,6 weeks of CUMS procedure induced the rats to a depression-like state,decreased weight and sucrose preference,and increased the expression of enzymes involved in vitamin D activation and catabolism (CYP27B1 and CYP24A1,respectively) and vitamin D receptor (VDR) in rat prefrontal cortex.As compared with CUMS group,CYP27B1,CYP24A1 and VDR were significantly decreased in CUMS+sertraline group (P<0.01 or P<0.05). Conclusion CUMS activates vitamin D signaling in the brain of the animal models of depression,while sertraline alleviates depressive behavior and relieves stress-induced activation of vitamin D signaling,indicating that vitamin D signaling may be involved in the stress-induced depression.
Objective To study absorption characteristic of dioscin from Dioscorea nipponica Makino extract in rat intestine. Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC was used to determine the concentrations of dioscin. The effects of different intestinal segments,drug concentration and P-glycoprotein (P-gp) inhibitor on intestinal absorption were investigated. Results Dioscin could be absorbed in the whole intestine,the absorption rate constant (Ka) and the apparent coefficient (Papp) of dioscin decreased following the sequence of ileum > duodenum = jejunum > colon.Absorption parameters of dioscin had no significant difference at different concentrations (40,80,120 mg·L-1).There were significant differences in Ka and Papp values between P-gp inhibitor group and no P-gp inhibitor group(P<0.05). Conclusion The saturate phenomena was not observed under the test range of drug concentration,and the absorption mechanism may be passive diffusion transport. Dioscin in Dioscorea nipponica Makino extract may be the substrate of P-gp.
Objective To develop a method for determination of serumal copper ion in rabbit with implantation of copper intrauterine device. Methods At different time points after implantation,the serumal copper ion concentrations were determined by microwave digestion-inductively coupled plasma mass spectrometry(ICP-MS) using scandium(Sc) and indium(In) as internal standards to compensate sample matrix effects,and the pharmacokinetics parameters were calculated in order to reflect copper ion release and metabolic rule. Results The serumal copper ion concentrations were kept at a low and stable level.The recoveries were in the range of 98.7%-113.3%,with the relative standard deviations of less than 5.0%. Conclusion The analytical method is simple,fast,and can be used for the determination of serumal copper ion in rabbit.
Objective To investigate the effect of Miao medicine Jinwu Jiangu decoction containing serum freeze-dried powder on levels of IL-17,ACT1 and TRAF6 in human rheumatoid arthritis fibroblast like synoviocytes (RA-HFLS). Methods Rabbits were randomly divided into blank control group (recieving normal saline of the same volume),Jinwu Jiangu decoction high-dose,medium-dose and low-dose group (intragastrically administrated with Jinwu Jiangu decoction at doses of 14.4,4.8 and 2.4 g·kg-1,respectively),tripterygium glycosides group and prednisone group (treated with human equivalent dosage).RA-HFLS primary cell model was established in the experiment.ELISA method was used to detect effect of lyophilized powder on IL-17 secretion.Expression of ACT1,TRAF6 mRNA was detected by RT-PCR. Results Compared with the blank control gorup,IL-17 in the supernatant of each medication administration group was significantly decreased (all P<0.01),and it was decreased most significantly in Jinwu Jiangu decoction high-dose and medium-dose group.IL-17 was down-regulated more significantly in high-dose group than that in tripterygium glycosides group (P<0.01).Compared with the blank control group,TRAF6 and ACT1 mRNA expression level of each medication administration group were significantly decreased (all P<0.01),and in the high-dose group that were decreased most significantly,but not significantly different as compared with tripterygium glycosides group and prednisone group (P>0.05). Conclusion Freeze-dried powder of Jinwu Jiangu decoction can decrease the secretion of IL-17 and down-regulate expression of ACT1,TRAF6 with RA-HFLS.
Objective To explore the changes of bone mineral density (BMD) and bone markers in senile osteoporosis patients treated with teriparatide,and evaluate the improvement on quality of life (QOL) as well as the clinical significance. Methods Forty-five senile osteoporosis inpatients were treated with 20 μg of teriparatide for one year. BMD and bone markers were detected before treatment and also in the third,sixth and twelfth month during treatment.The level of numerical rating scale (NRS) and QOL were assessed. Results The NRS before treatment was (4.96±2.25) , and those after treatment of 3, 6 and 12 months were(2.84±1.41), (1.56±1.16) and (1.36±1.00), respectively (P<0.01). The total scores of SF-36 significantly increased after treatment (P<0.01). After treatment of 3, 6 and 12 months, BMD of lumbar vertebra had increased 7.7%, 12.3% and 15.4%, respectively; that of femoral neck had increased 3.0%, 6.1% and 7.6%, respectively; and that of intertrochanteric bone had increased 5.7%, 8.6% and 10.0%, respectively. Meanwhile, the serum levels of osteocalcin, bone alkaline phosphatase and N terminal propeptide of type I procollagen were significantly higher than those before treatment (P<0.01), nevertheless beta collagen cross-linked C-terminal peptide (β-CTX) only significantly decreased at the 12th month after treatment (P<0.05). Conclusion Chronic teriparatide therapy could significantly relieve bone pain,improve the quality of life and increase lumbar vertebra BMD in senile osteoporosis.
Objective To investigate the medical effect of the ethanol extract of Acorus gramineus Sol.on arthritis of mice induced by collagen-Ⅱ,and explore the potential pharmacological mechanisms. Methods Arthritis mouse model was established by injection of admixture containing type Ⅱ collagen and Freund's complete adjuvant (FCA) in male BALB/c mice.Mice were divided into five groups:the normal control group (0.9% of sodium chloride solution),the model control group (0.9% of sodium chloride solution),tripterygium group (15 μg·kg-1 of tripterygium tablets), the high-dose of extract of Acorus gramineus Sol. group (60 mg·kg-1 extract of Acorus gramineus Sol.) and the low-dose of extract of Acorus gramineus Sol. group (15 mg·kg-1 extract of Acorus gramineus Sol.).Each group was administered once a day,lasting 21 days.During the experiment,ankles of all mice were measured at predetermined time.At the end of the experiment,blood of the mice was exsanguinated and centrifuged to get serum for measuring the levels of IL-1β,RF and TNF-α.Spleens of mice were dissected and weighed to calculate the spleen index.All arthritis ankles were dissected to make tissue section,and observed under microscope. Results Compared with the model control group,the perimeter of ankle joints of the high-dose of extract of Acorus gramineus Sol. group significantly changed 6 days after administration (P<0.05); That of the low-dose of extract of Acorus gramineus Sol.group significantly changed 12 days after administration (P<0.05); That of tripterygium group significantly changed 9 days after administration (P<0.05).As compared with the normal control group, the spleen index of the model control group was significantly different (P<0.01).As compared with the model control group,the spleen index of tripterygium group,high-dose and low-dose of extract of Acorus gramineus Sol.groups were significantly different (P<0.05).As compared with the normal control group,levels of IL-1β,RF and TNF-α of the model control group were significantly different (all P<0.01).As compared with the model control group,levels of IL-1β,RF and TNF-α of tripterygium group,high-dose and low-dose of extract of Acorus gramineus Sol.groups were significantly decreased. Conclusion Ethanol extracts of Acorus gramineus Sol. have significant therapeutic effect on arthritis mice.The anti-arthritic mechanism is associated with its ability to regulate levels of IL-1β,RF and TNF-α.
Objective To explore the effects of the heterocyclic oleanolic acid derivatives-aspirin conjugates on inhibition of serotonin biosynthesis and increase of bone formation. Methods The inhibition rate,content and mRNA expression of heterocyclic oleanolic acid derivatives-aspirin conjugates on tryptophan hydroxylase 1 (TPH-1),which was the principal enzyme in the biosynthesis of serotonin,were tested by HPLC,ELISA kit and real-time PCR,respectively.Osteoporosis model was established by ovariectomy (OVX).The rats were randomly divided into conjugate groups,parathyroid hormone group,model control group and sham operation group.Serum and gut serotonin levels were tested by HPLC after 35 days of administration,and the antiosteoporosis activity of the heterocyclic oleanolic acid derivatives-aspirin conjugates was evaluated by using osteoblast-like cells isolated from murine calvaria by MTT assay. Results The preliminary biological results showed that heterocyclic oleanolic acid derivatives-aspirin conjugates displayed a dose-dependent suppression on TPH-1 in RBL-2H3,and the inhibition rate was 20.4%-92.5%.Specifically,conjugate 7 at 10 μmol·L-1 concentration showed the greatest inhibition rate on TPH-1 (92.5%).Content of TPH-1 was 51 ng mL-1,significantly lower than that in the control group (216 ng·mL-1),as well as the TPH-1 mRNA.Compared with the sham operation group,levels of serum and gut serotonin were increased in OVX group,while they were significanlty decreased in conjugate groups,and reduced significantly in conjugate 7 group (232 and 155 ng·mL-1) as compared with OVX group (1 050 and 783 ng·mL-1); Moreover,heterocyclic oleanolic acid derivatives-aspirin conjugates could increase the bone formation. Conclusion This study provides information and basis for development of novel,efficient and harmfulless oleanolic acid derivatives with anti-osteoporosis.
Objective To evaluate the effects and safety of total glucosides of paeony (TGP) in the treatment of patients with Sjogren syndrome. Methods The Cochrane Library,PubMed,EMBASE,CBM,VIP,CNKI,Wanfang databases were searched from their establishments up to September 30,2015.We used the method recommended by the Cochrane collaboration to perform a meta-analysis of randomized controlled trails (RCTs) of total glucosides of peony in the treatment of patients with Sjogren syndrome.Two reviewers analyzed these data independently.The Cochrane Collaboration's software RevMan 5.3 was used for meta-analysis. Results A total of 573 patients in 10 studies were finally included,and were divided into different subgroups.The results of subgroup-analysis showed that:①Schimer test:TGP group had a higher effective rate than the blank control group [MD=2.41,95%CI (0.08,4.74)],lower effective rate than Chinese herbal medicine [MD=-2.55,95%CI (-3.88,-1.22); ②Salivary flow:TGP group had a lower effective rate than the control group [SMD=-0.87,95%CI (-1.20,-0.54)].③Rheumatic factors (RF):TGP group had a higher effective rate than Chinese herbal medicine [SMD=0.44,95%CI (0.06,0.82)] and Chinese patent drug [SMD=0.74,95%CI (0.36,1.12)],lower effective rate than the blank control group [SMD=2.23,95%CI (-2.79,-1.67); ④ C-reactive protein (CRP):TGP group had a higher effective rate than the control group [MD=4.51,95%CI (1.75,7.26)]; ⑤IgG:TGP group had a higher effective rate than Chinese patent drug group [MD=2.73,95%CI (1.63,3.84)],lower effective rate than the blank control group [MD=-3.90,95%CI (-5.67,-2.13),but no statistical difference was noted when compared with Chinese herbal medicine and Western medicine groups; ⑥ESR:TGP group had a higher effective rate than Chinese herbal medicine group [MD=12.73,95%CI (3.62,21.84)] and Chinese patent drug group [MD=7.82,95%CI (5.39,10.24)],lower effective rate than the blank control group [MD=-7.13,95%CI (-12.70,-1.56) and Western medicine group [MD=-12.19,95%CI (-24.19,-0.19)]; ⑦Safety:8 studies reported adverse effects in 41 patients.TGP group had a higher adverse reaction rate than the control group [OR=3.23,95%CI (1.60,6.50)]. Conclusion Current evidence demonstrates that TGP can effectively improve CRP,but its effects on Salivary flow,Schimer test,IgG,ESR,RF were not significant.However,the heterogeneity and high risk of bias in the reports involved in this study limits the reliability of this conclusion.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by polyarthritis.Numerous agents with varying mechanisms are used in the treatment of RA,but there is no radical cure.Interleukin-6 (IL-6) plays an important role in the pathogenesis of RA.Agents targeting IL-6 such as tocilizumab (TCZ) attracted significant attention as a promising agent in RA treatment.This article reviewed the key efficacy and safety data from clinical trials of TCZ,as well as six candidate IL-6 blockers including sarilumab,ALX-0061,sirukumab,MEDI5117,clazakizumab,and olokizumab,and their future perspectives in the treatment of RA.
Objective To observe the effects of berberine on neuralogical function,serum oxidized low density lipoprotein(ox-LDL),and matrix metalloproteinases-9(MMP-9) in patients with acute cerebral infarction. Methods Ninety-two patients with acute cerebral infarction were randomly divided into treatment group and control group (n=46).Control group received routine treatment,while treatment group was given 0.3 g of berberine three times a day besides routine treatment for 14 days.In both groups,decubitus venous blood was harvested before,7 and 14 days after treatment.Serum ox-LDL and MMP-9 were determined with enzyme-linked immunosorbent assay (ELISA).Before and 7 and 14 days after treatment,the neural function defect was graded by the US National Institutes of health stroke scale (NIHSS) and the modified Rankin scale (mRS). Results The neurological function was improved significantly in 7 and 14 days after the treatment for both two groups according to NIHSS and mRS,and the difference between treatment group and control group was statistically significant (P<0.05).After treatment,ox-LDL and MMP-9 declined significantly in both groups,and were lower in treatment group than in control group (all P<0.05). Conclusion Berberine significantly reduces ox-LDL and MMP-9 levels in patients with acute cerebral infarction and improves the degree of neurological function deficit.
Nanometer material have been widely used in a number of fields because of their diversified physical and chemical effects.Owing to their good biocompatibility,well targeting property and high bioavailability,they are considered as a good support for vaccine adjuvant.In short,it has a targeting function to specific parts,can improve the immunogenicity of new vaccine,avoid first-pass metabolism in the liver and then has less side effect.With these advantages,it has shown a proved potential application for disease control and treatment.So some unique properties of nano-materials are reviewed,with a look forward to the future of their application technology in the areas of and medicine.
Objective To explore the feasibility of using the quantitative reference extract of ginkgo leaf total lactones instead of single component reference for the quantitative assay of Ginkgo Folium. Methods HPLC-ELSD method was performed by using a Diamonsil C18 column (250 mm×4.6 mm,5 μm) with methanol-water as the mobile phase at the gradient elution mode.Flow rate was 1.0 mL·min-1.The parameters of ELSD detector were as follows,the drifit tube temperature was 105 ℃,and the flow rate of nitrogen(N2) was 3 L·min-1. Results The linear ranges of ginkgolide A,ginkgolide B,ginkgolide C,and bilobalide were 0.735-5.879 μg (r=0.999 6),0.404-6.060 μg (r=0.999 6),0.296-4.439 μg (r=0.999 6),and 1.001-6.006 μg (r=0.999 7),respectively.The recoveries and RSD of the four components were 95.6% (4.0%),97.3% (4.5%),99.3% (5.0%),and 100.4% (2.1%),respectively. Conclusion The quantitative reference extract of ginkgo leaf total lactones can be used as the substitute for the determination of terpene lactones.
Objective To explore the extraction process of Yinxing Huonao capusle. Methods Central composite design-response surface method was used to optimize the extraction process with quantity of water and boiling time as main factors and with syringin transfer rate,emodin transfer rate and solids retention rate as evaluation index. Results The conditions of the optimized extraction process were as follows:10-fold water,extracting time of 160 min,extracting 2 times. Conclusion It is feasible that central composite design-response surface method is used to optimize the extraction process of Yinxing Huonao capusle,and the optimized extraction process is simple and reliable.
Objective To determine the triterpenoid content in Loquat leaf by using HPLC method and to explore the feasibility of ursolic acid and oleanolic acid as the quantitative markers for determination of Loquat leaf and its preparations. Methods Two desugaring methods of Loquat leaf extracts were compared.The contents of ursolic acid and oleanolic acid in Loquat leaf as well as preparations were measured based on a system of HPLC,with a Dumas Diamonsil C18 column (250 mm×4.6 mm,5 μm) was used as analytical column.The mobile phase was consisted of acetonitrile -0.1% phosphoric acid (95∶5) with the flow rate of 0.5 mL·min-1.The column temperature was 30 ℃,the injection volume was 10 μL, the detective wavelength was 210 nm. Results Ursolic acid and oleanolic acid were measured in both Loquat leaf and its preparations,and their contents were fairy stable and comparable. Conclusion Ursolic acid and oleanolic acid can be served as quantitative markers for the determination of Loquat leaf and its preparations.
Objective To investigate the distribution and susceptibility of isolated organisms from blood of malignant tumour patients. Methods Isolates from blood culture in patients with cancer during January 2013 to December 2015 were analyzed.Results were analyzed according to the breakpoints of CLSI 2014. Results Total of 498 isolates from blood culture,gram-negative bacilli accounted for 58.0% and gram-positive cocci accounted for 42.0%.The most common pathogens were E.coli,Coagulase-negative Staphylococcus,Klebsiella spp, S.aureus and Enterococcus spp. Drug resistance of E.coli strains to piperacillin-tazobactam,amikacin and imipenem were low,and drug resistance of E.coli strains to ampicillin-sulbactam,gentamicin,ciprofloxacin,levofloxacin and compound sulfamethoxazole were high.The prevalence of ESBL-producing strains was 70.7% in E.coli and 22.8% in Klebsiella spp.The E.coli and Klebsiella spp.strains isolated from ICU showed higher resistance than the strains from surgery and medicine department.The E.faecium strains were highly susceptible to gentamicin (high level) and lower susceptible to most of the antibiotics tested.The E.faecalis strains were more susceptible than E.faecium to these agents.No vancomycin-resistant strains were found in Enterococcus spp. Conclusion Among gram-negative pathogen isolates from blood culture in cancer patients,E.coli and Klebsiella spp. are the most frequent.Staphylococcus and Enterococcus are the most frequently isolated species of gram-positive cocci.The percentage of Acinetobacter spp.strains is relatively higher in ICU.Surveillance of antimicrobial resistance can provide the basis for rational use of antibiotics.
Objective To systematically evaluate the efficacy and safety of alprostadil injection in patients with viral hepatitis. Methods Medline,Embase,The Cochrane Library,CBMdisc,CNKI,Wanfang Database and VIP were searched.The quality of included studies such as randomization,blinding,allocation concealment and loss of follow-up were evaluated and meta-analysis was performed by RevMan5.1 software. Results In total,14 RCTs and 1 232 patients were included.Meta-analysis showed that in patients with viral hepatitis,the total effective rate of alprostadil injection treatment was significantly superior to that of conventional therapy (P<0.000 01).Serious adverse drug reactions (ADRs) induced by alprostadil injection were not reported. Conclusion Alprostadil injection is effective and safe for treating viral hepatitis.However,the evidence is not strong due to the generally low methodological quality of RCTs.Further high quality and large sample-sized randomized controlled trials and more pharmacoeconomics studies should be carried out.
Objective To explore the medication closed-loop management of huangshi central hospital based on electronic medical records. Methods Diversified pharmaceutical information platform was constructed.The full coverage of all aspects of medication information,such as ordering/prescribing,transcribing,distributing,preparing,dispensing,administering,documenting,and monitoring was realized. Results The medication management and use had no information gap,and bias could be controlled to form a closed-loop management. Conclusion Application of the new information technology in the field of pharmaceutical care can improve work efficiency,reduce medication errors,broaden the vision of clinical pharmacists and scope of work,and improve the overall level of pharmaceutical care.