OBJECTIVE： To introduce Pharmaceutical Care Network Europe （PCNE） classification system to develop medication therapy management （MTM）， and to investigate the application of PCNE classification system in solving drug-related problems （DRPs） in type 2 diabetic patients and the effect of it on clinical outcomes. METHODS： The patients with type 2 diabetes diagnosed in endocrinology department of our hospital from Jul. 10， 2018 to Oct. 31， 2018 were randomly divided into clinical pharmacist-led intervention （“physician-pharmacist-nurse” mode） group and control group receiving only traditional medical services （“physician-nurse” mode）. According to PCNE classification， the number of DRPs found in the pharmaceutical intervention group， the types of problems， causes， the types of interventions， acceptance for interventions and outcomes were analyzed and evaluated. Drug compliance （the highest score is 8） and HbA1c compliance （＜7％） were compared between 2 groups during hospitalization （or at the discharge） and 3 months after discharge. RESULTS： Totally 76 cases were included （40 cases in pharmaceutical intervention group and 36 cases in control group）. During hospitalization， 51 DRPs were found in the pharmaceutical intervention group， among which 42 problems were related to the effectiveness of treatment， mainly due to improper usage and dosage （23 problems）； the types of intervention was mainly aimed at the patient level （24 problems）. 38 problems received intervention （acceptance rate was 74.51％） and 32 problems （62.75％） were completely solved. Compared with those at admission， after following up for 3 months patients with low score （6 points） in the drug compliance of the pharmaceutical intervention group decreased from 26 to 8 （P＜0.000 1）， patients with medium score （6-8 points） increased from 10 to 22 （P＝0.006 2）， patients with high score （8 points） increased from 4 to 10， and drug compliance improved significantly， while there was no significant change in drug compliance in the control group. Compared with those at the discharge， after 3 months’ follow-up， the HbA1c compliance rate of the pharmaceutical intervention group increased from 25.00％ to 77.50％， and that of the control group increased from 25.00％ to 55.56％. There were statistical differences （P＜0.000 1）， and HbA1c compliance rate of the pharmaceutical intervention group was significantly higher than that of the control group. CONCLUSIONS： In the practice of MTM service， clinical pharmacists use PCNE classification system to collect， analyze， intervene， solve and evaluate DRPs systematically. The service mode can provide reference for standardizing pharmaceutical care mode.

OBJECTIVE: To develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of atorvastatin and voriconazole in rat plasma and investigate the pharmacokinetics of atorvastatin and the changes in voriconazole concentration in rats after administration. METHODS: Plasma samples were collected from rats after intragastric administration of atorvastatin alone or in combination with voriconazole. The samples were treated with sodium acetate acidification, and atorvastatin and voriconazole in the plasma were extracted using a liquidliquid extraction method with methyl tert-butyl ether as the extractant. The extracts were then separated on a Thermo Hypersil Gold C18 (2.1×100 mm, 1.9 μm) column within 6 min with gradient elution using acetonitrile and water (containing 0.1% formic acid) as the mobile phase; mass spectrometry detection was achieved in selective reaction monitoring (SRM) mode under the positive ion scanning mode of heated electrospray ion source (H-ESI) and using transition mass of m/z 559.2→440.2 for atorvastatin and m/z 350→280 for voriconazole, with m/z370.2→252 for lansoprazole (the internal standard) as the quantitative ion. RESULTS: The calibration curves were linear within the concentration range of 0.01-100 ng/mL (=0.9957) for atorvastatin and 0.025-100 ng/mL (=0.9966) for voriconazole. The intra-day and inter-day precisions were all less than 13%, and the recovery was between 66.50% and 82.67%; the stability of the plasma samples met the requirements of testing. The AUC of atorvastatin in rat plasma after single and combined administration was 438.78±139.61 and 927.43±204.12 h·μg·L, CLz/F was 23.89±8.14 and 10.43±2.58 L·h·kg, C was 149.62±131.10 and 159.37±36.83 μg/L, t was 5.08±1.63 and (5.58±2.11 h, and T was 0.37±0.14 and 3.60±1.52 h, respectively; AUC, CLZ/F and T of atorvastatin in rat plasma differed significantly between single and combined administration. The HPLC-MS/MS system also allowed simultaneous determination of voriconazole concentration in rat plasma after combined administration. CONCLUSIONS The HPLC-MS/MS system we established in this study is simple, rapid and sensitive and allows simultaneous determination of atorvastatin and voriconazole in rat plasma. Some pharmacokinetic parameters of atorvastatin are changed in the presence of voriconazole, and their clinical significance needs further investigation.
Administration, Oral ; Animals ; Atorvastatin ; Chromatography, High Pressure Liquid ; Rats ; Tandem Mass Spectrometry ; Voriconazole

OBJECTIVETo observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms.

METHODSHigh-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry.

RESULTSThe major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P(P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P(P<0.05) in rats following nephrectomy.

CONCLUSIONSCompound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Fibronectins ; metabolism ; Fibrosis ; Intercellular Adhesion Molecule-1 ; metabolism ; Kidney ; pathology ; Kidney Failure, Chronic ; drug therapy ; Nephrectomy ; Rats

Objective To observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms. Methods High-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry. Results The major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P<0.05) in rats following nephrectomy. Conclusion Compound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.

Objective To observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms. Methods High-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry. Results The major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P<0.05) in rats following nephrectomy. Conclusion Compound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.

OBJECTIVE:To establish atomic absorption spectrometry for the assaying of the microelement manganese in Changtong oral liquid.METHODS:The light source was hollow-cathode lamp with wavelength at 279.5nm,the electric current of the light was 3.0mA,the slit-width was 1.2nm,the air flow rate was 5.0L/min and the flow rate of acetylene was 1.0L/min.RESULTS:The calibration curves was in linear correlation with adsorption when the detection concentration range of manganese was 0.5～2.5?g/ml(r=0.9 997),the average recovery was 99.24%(RSD=2.06%,n=5).CONCLUSION:This method is simple,fast,accurate,sensitive and precise.

OBJECTIVE: To prepare Mitomycin C for injection-Polybutylcyanoacrylate Nanoparticles (MMC-PBCA-NPs) freeze drying preparation by microfluidization and to investigate its hemolytic feature. METHODS: The crude emulsion of MMC-PBCA-NPs was prepared by emulsion polymerization method, from which MMC-PBCA-NPs solution was prepared by microfluidization method; the encapsulation efficiency (EE) and the drug loading (DD) of the preparation were detected by ultraviolet spectrophotometry. The particle size and appearances of which were observed. A hemolytic test was performed on rabbits to observe the blood reaction of the preparation. RESULTS: The prepared MMC-PBCA-NPs freeze drying preparation was uniformly distributed and in round shape, with EE, DD and mean diameter at (85.1?3.8)%, (7.0?0.2)% and (113.5?3.86)nm, respectively. The hemolytic test was negative. CONCLUSION: It is feasible to prepare MMC-PBCA-NPs by microfluidization method.

Objective To optimize the preparation of nanoparticles encapsulating antisense oligodeoxynucleotides in a-butyleyanoacrylate carrier (ASODN in NP) and investigate their stability. Methods ASODN in NP were prepared by interfacial polymerization of butyleyanoacrylate (BCA). The formulation and technology of the prepared NP was optimized by using orthogonal design based on the single-factor experiment. The morphology of NP was examined by transmission electron microscope; The size and size distribution of NP were determined by Malvern laser granularity equipment;The encapsulation efficiency and drug loading were determined by HPLC; The ability of protecting oligodeoxynucleotides from serum was investigated on a 20% polyacrylamide-7 Murea sequencing gel (PAGE). Results The nanoparticles in the optimal conditions were of regular spherical surface and discrete. The average size was 97.1 nm,the average encapsulation efficiency and drug loading of ASODN in NP were 96.7% and 10.1% respectively; The oligonucleotides were more efficiently protected from degradation by nucleases than by oligonucleotides adsorbed into nanospheres.Conclusion ASODN in NP has good stability,encapsulation efficiency,drug loading and great potential for ASODN delivery.

MF.

Aim To investigate the influence of skin layers ( st ratum corneum and viable layer) on the percutaneous absorption of drug with or w ithout isopropyl myristate (IPM). Methods We chose theophylline (TP ) as a model drug. Patches containing saturated concentration of TP were prepare d. The in vitrotransdermal permeation experiment via different rat skin lay ers was carried out. Results The Kp of TP via stripped skin was 2.1 times larger than that via intact skin. The permea bility was en hanced when coexisted with IPM either via intact skin or via stripped skin. Conclusion IPM can significantly enhance the percutaneous absorption of TP via different skin layers. And these data and methods represent a novel appr oach to evaluate the effects of skin damage and skin disease on drug percutaneou s absorption.