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??Chinese Pharmacopoeia (Ch.P) 2015 edition is the 10th revision of Ch.P since the People??s Republic of China was established.The article is to describe the general situation about the development of Ch.P 2015 edition, it will play very important role for the Ch.P 2015 on improving the standards system, strengthening the quality control for the drug, increasing the application of the advance detection technology, enlarging the monographs adoption, Improving the general requirements and control for the drug safety as well as the leading the international drug standards.     

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??OBJECTIVE To study the chemical constituents of Erigeron annuus (L.) Pers.. METHODS The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, Sephadex LH-20, MCI Gel CHP-20, silica gel column chromatography, and preparative HPLC, and their structures were elucidated on the basis of spectral data and physiochemical properties. RESULTS Twenty compounds were elucidated as vanillic acid(1), ferulic acid(2), 4-hydroxyacetophenone(3), dihydroconiferylalcohol(4), loliolide(5), 4-hydroxy-3-methoxyphenylprop-8-ene 4-O-??-D-xylopyraosyl-(1??6)-??-D-glucopyranoside(6), 1H-indole-3-carbaldehyde(7), 5,7-dihydroxychromone(8), pyromeconic acid(9), erigeside D(10), methyl syringate 4-O-??-D-glucopyranoside(11),(7S,8R)-urolignoside(12), homoeriodictyol(13), pinobaksin(14), chrysin(15), hispidulin(16), chryseriol(17), cyclomorusin(18), cirsimaritin(19), and naringenin(20), respectively. CONCLUSION Compounds 1-8 and 11-19 is isolated from this plant for the first time.     

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??OBJECTIVE To discuss the problem of instrumental test method of clarity and degree of opalescence of liquids in the general notice 0902 of China Pharmacopeia(Ch.P)2015, find out the causes and offer solutions. METHODS The test methods of clarity in Ch.P 2015 and European Pharmacopeia (EP) 8.0 were compared, including instrumental types, applicability, sample requirements, and result evaluation. RESULTS The primary opalescent suspension for the instrumental method is the same as the visual method, using the absorbance (A=0.12-0.15) at 550 nm to control the opalescence. Because the resolving power of the instrumental method is far higher than the visual method, the limit becomes interval distribution instead of simple point. The opalescent value (NTU) of the upper limit (A=0.15) is about 1.35 times of the lower limit (A=0.12).When the NTU value of the test liquid is in this interval, the result evaluation will be hard.CONCLUSION The preparation of the primary opalescent suspension in Ch.P 2015 is different from EP8.0. For this reason, the limit set by Ch.P 2015 is actually stricter than that of EP8.0. The opalescent value of the standard solution used by Ch.P 2015 is about 75% of that used by EP8.0.     

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??OBJECTIVE To synthesize the impurity A of sitagliptin which is a highly selective DPP-4 inhibitor used for treatment of type 2 diabetes. METHODS 1-{3-Trifluoromethyl-5,6-dihydro-1,2,4-triazo[4,3-a]piperazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)butane-1,3-dione was prepared from 2,4,5-triflurophenylacetic acid, meldrum's acid and 3-trifluromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine hydrochloride with one-pot reaction, followed by reduction with sodium borohydride to yield the impurity A of sitagliptin. RESULTS The structure of the impurity A of sitagliptin was characterized by IR, MS, and ¹H-NMR. CONCLUSION The established synthetic route of the impurity A in this study has not been reported in the literature, and has the advantages of low-cost, easy operation, mild reaction, and high overall yield.     

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??OBJECTIVE To select the fungi which can induce Dalbergia odorifera to produce active substances. METHODS Twenty-five fungi were inoculated in the stems of six or seven-year-old D. odorifera under natural conditions. Fungi with biological activity to induce D. odorifera producing active substances were obtained through field screening and chemical quality evaluation. The ethanol-soluble extractives and total flavonoids of D. odorifera were analyzed by spectrophotometry and hot maceration method, respectively. RESULTS Six active fungi inducing the formation of heartwood were obtained. CONCLUSION This study is very important for utilizing fungi in the induction of D. odorifera and sustainable utilization of this special medicinal material.     

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??OBJECTIVE To establish a detection method based on a novel type of two-dimensional liquid chromatographic system (2D-LC-UV) for determination of paraquat in poisoned patients' urine, and assess the methodology and characteristics of the two-dimensional chromatography. METHODS 2D-LC-UV contains 1st and 2nd liquid chromatography and FLC transferor. Urine sample of 100 ??L was directly injected without pretreatments, and paraquat was on-line concentrated and primarily separated on the 1^st Aston SX1 column, then trapped on Aston SX column and separated by Aston SX1 column. The mobile phase of the 1st liquid chromatography, trapping column and 2nd liquid chromatography were acetonitrile-2 mol??L^-1 ammonium acetate binary solution(1:10, V:V, 1.0 mL??min^-1), pure water and 2.5 mol??L^-1 ammonium acetate solution-methanol-acetonitrile ternary system (5:3:1, V:V:V, 1.0 mL??min^-1), respectively. The column temperature was maitained at 40 ??, and the UV adsorption wave length was set at 285 nm. RESULTS The chromatographic system was capable of processing 500 ??L urine. Paraquat was transferred and separated completely in the two-dimensional system with linear calibration curve over the concentration range of 20-20 000 ng??mL^-1 (r=0.999 9). The urine matrixes from different samples had little interference effect. The chromatographic balance time was less than 15 min, and the calibration curve was stable for more than 90 d. CONCLUSION Because of its accuracy, stability, automation, and independence of specialized technical personnel, the established chromatographic method is ideal for quick test of paraquat in poisoned patients, providing scientific basis for clinical treatment of patients with paraquat poisoning.     

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??OBJECTIVE To compare the setting methods for biologics data protection period between America and Japan, in order to provide suggestions for China. METHODS We made a contrastive study of American ??break even?? model and Japanese ??risk management evaluation?? model by using method introduction and characteristic analysis. RESULTS The two setting methods in the US and Japan focus on different system objectives, respectively. The Chinese choice of setting method needs to combine the feasibility of setting methods and the national conditions and policy goals for comprehensive consideration. CONCLUSION At present and the future for a long time, China's pharmaceutical industry is still in the ??imitation to innovation?? stage, and drug safety issues remain the core task. Therefore, the period of biologics data protection should be rationally set up by using ??risk management evaluation?? model as the base, ??break even?? model as supplement, so as to bring the three policy effects such as innovation incentive, the improvement of innovative drugs availability and strengthening the drug post-market safety monitoring.     

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??OBJECTIVE To study the chemical constituents from the fruits of Lycium ruthenicum Murr. METHODS The compounds were isolated by various chromatographic METHODS including macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 column chromatography, and preparative HPLC, and their structures were elucidated on the basis of spectroscopic data and physico-chemical METHODS. RESULTS Eleven compounds were isolated from the 65% ethanol extract of the fruits of Lycium ruthenicun Murr., and their structures were identified as p-hydroxyphenethyl trans-ferulate(1), kaempferol 3-O-??-D-glucopyranoside(2), quercetin 3-O-??-D-glucopyranoside(3), syringin(4), quercetin(5), ethyl caffeate(6), p-coumaric acid(7), ferulic acid(8), 2,6-bis(1-phenylethyl) phenol(9), dotriacontane(10), and daucosterol(11). CONCLUSION Compounds 1-4, 6, 9, and 10 are for the first time isolated from Lycium ruthenicum Murr. Compounds 1-8 show moderate protective effects on OGD-induced PC12 cell lines.     

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??OBJECTIVE To establish a method for the determination of norathyriol in rat plasma by HPLC and to study its characteristics of pharmacokinetics. METHODS Ethyl formic acid(10:1)was used to precipitate protein in the plasma samples after the addition of internal standard, and then the concentration was analyzed by HPLC. All of the separations were carried out on a Platisil ODS(4.6 mm??250 mm,5 ??m) at room temperature. The mobile phase was consisted of formic acid(40:60:0.5, pH 2.74), and was pumped at flow rate of 0.8 mL??min^-1. The UV detection wavelength was set at 312 nm. The rats were given norathriol by intragastric administration with a dosage of 400 mg??kg^-1. The concentration of norathriol in plasma at different time points was determined. RESULTS A good linear relationship was obtained in the concentration range of 0.54-162 ??g??mL^-1(r=0.998). The intra-day and inter-day RSD were less than 7.5% . The main pharmacokinetic parameters measured by Winnonlin 6.1 were showed as follows:t_max,t_1/2, ??_max and AUC_0-t were 0.5 h,(3.46??0.903) h,(26.9??3.17)??g??mL^-1,(52.4??12.0) ??g??h??mL^-1, respectively. CONCLUSION The HPLC method established is rapid and specific, and can be successfully applied in basic pharmacokinetic study in rat plasma.     

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??In situ gel is liquid upon instillation and undergo phase transition under physiological conditions to form visco-elastic gel with dual advantages of liquid and gel.Ordinary eye drops exist a problem of short residence time with low bioavailability. In recent years, an impressive number of novel in situ gel systems have been reported for ocular drug delivery to increase bioavailability with the extension of corneal residence time. In this article, the classification and application about in situ gel for ocular drug delivery are reviewed, then the study status and the key technical problem of the in situ ophthalmic gel in detail are described. In addition, the future advancement of this field is also discussed.     

新型眼用硝酸毛果芸香碱六角液晶凝胶的制备和评价

目的 本研究以硝酸毛果芸香碱(PN)为模型药,以植烷三醇(PHYT)/三辛酸甘油酯(TAG)/水三元系统制备六角相液晶(HⅡ)凝胶,通过眼部给药提高PN的眼用生物利用度.方法 采用偏光显微镜(CPLM)、小角X射线散射仪(SAXS)和流变学对HⅡ凝胶的内部结构进行表征;通过体外释放和离体角膜渗透对HⅡ凝胶的体外行为进行...     

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??OBJECTIVE To prepare lappaconitine(LA)-loaded chitosan/ sodium ??-glycerophosphate(CS/??-GP) thermosensitive hydrogels and investigate its phase transition mechanism of gel formation process and release properties in vitro. METHODS The injectable CS/??-GP thermosensitive hydrogels were prepared with biodegradable CS as carrier material and ??-GP as coagulation accelerator. The release behavior in vitro was studied by dynamic dialysis, and the phase transition mechanism of gel formation process was further investigated by rheological method. RESULTS The optimized process condition was as follows:the concentration of ??-GP and CS was 560 and 22 mg??mL^-1, respectively, CS was dissolved by 0.1 mol??L^-1 HOAc, and the valume ratio of CS to ??-GP was 8.75??1.25(V/V), the gelation time of CS/??-GP thermosensitive hydrogels with volume ratio of 8.75??1.25(V/V) at 37 ?? was 5 min 38 s. The in vitro release study showed that these injectable CS/??-GP thermosensitive hydrogels had sustained release effect for LA, and the release behavior could be well described by the Higuchi model and Korsmeyer-Peppas model. The mechanism of LA releasing from CS/??-GP thermosensitive hydrogels was attributed to drug dissolution and diffusion. Rheological studies showed that the CS/??-GP thermosensitive hydrogels belonged to thixotropic system and exhibited non-Newtonian and shear-thinning fluid behavior as well as ??solid-like?? gelatin behavior. CONCLUSION LA-Loaded CS/??-GP injectable thermosensitive hydrogels with good elasticity and gel strength properties are prepared successfully, and they show sustained release effect of LA in vitro.     

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??OBJECTIVE To prepare and characterize sinomenine liquid crystal gel, study the rheological properties and in vitro transdermal properties and compare with sinomenine ointment and sinomenine hydrophilic gel. METHODS Sinomenine liquid crystal gel was prepared by using phytanetriol-water system and then characterized by polarized light microscope(PLM)and small angle X-ray diffraction(SAXS). Using DHR-2 rheometer,the rheological properties of sinomenine liquid crystal gel were investigated and compared with those of sinomenine ointment and sinomenine hydrophilic gel. Modified Franz diffusion cell was used for in vitro transdermal experiment and the in vitro transdermal properties were compared with sinomenine hydrogels and ointments. RESULTS The appearance of sinomenine liquid crystal gel was colorless, clear and transparent, and showed dark field under PLM. SAXS showed cubic phase. The rheological parameters were good. The steady-state infiltration rates of sinomenine liquid crystal gel, ointment and hydrophilic gel were 153.93, 119.99, and 106.89 ??g??cm^-2??h^-1,and their 48 h cumulative permeation amounts(%)were 93.76%,91.55%, and 87.60%, respectively. CONCLUSION PLM and SAXS can be used to characterize the liquid crystal gel.The prepared sinomenine liquid crystal gel has good appearance and suitable rheology, and its infiltration rate and 48 h cumulative permeation amount are superior to those of ointment and hydrophilic gel, which provides theoretical reference for sinomenine percutaneous administration.     

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??OBJECTIVE To optimize the formula of celecoxib gel by studying the effects of different doses of penetration enhancers on the penetration of celecoxib through skin in vitro. METHODS With sodium alginate as the gel base, factorial design method was used to choose the optimal formula of penetration enhancers among four different formulas to prepare celecoxib gels. The release rate of celecoxib in the release media was detected by modified Franz diffusion cells method, and the steady percutaneous speed (J), permeability coefficient (K_p) and the accumulative permeation quantity (Q) in 12 h were calculated. RESULTS The accumulative permeation quantity (Q) in 12 h of celecoxib from the gels made with the four different formulas were 27.93,25.12,18.79 and 19.35 ??g??cm^-2, respectively. The gel with 1% azone and 1% menthol as penetration enhancers had the maximum Q value, 27.93 ??g??cm^-2, its penetration process conformed to Higuchi equation, and the steady percutaneous speed (J) and permeability coefficient(K_p)were also higher than the other three experimental groups. CONCLUSION With sodium alginate as the gel base, azone and menthol have a synergistic effect on the percutaneous penetration of celecoxib gels, and the best formula is 1% azone and 1% menthol.     

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??OBJECTIVE To prepare docetaxel liposomes by freeze-drying of tert-butyl alcohol (TBA)/water cosolvent system and evaluate the in vitro and in vivo properties. METHODS The formulation was optimized by single factor screening experiments. The effects of TBA/water ratio, lipid/drug ratio, sucrose/lipid ratio and mixing temperature on encapsulation efficiency were investigated. The in vitro release profiles were also investigated with docetaxel injection(Duopafei^?k) as control. RESULTS The formulated liposomes had a mean size of 263 nm with entrapment efficiency of (88.45??1.63)% at TBA/water ratio 50??50, lipid/ drug ratio 10??1, sucrose/lipid ratio 5??1 and mixing temperature 60 ??. In vitro drug release from liposomes lasted for 48 h. CONCLUSION Freeze-drying of TBA/water cosolvent system method may be feasible to prepare docetaxel liposomes.     

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??OBJECTIVE To study evodiamine complex nanoemulsion oil-in-water (EPBCN) in vitro and in vivo evaluation, about release in vitro and pharmacokinetics. METHODS Release in pH 1.2 hydrochloric acid and pH 6.8 PBS solutions and oral bioavailability in rats of EPBCN would be studied. The bioequivalence between evodiamine (ED) and EPBCN was judged. RESULTS In vitro release of EPBCN was about 2.61 times higher than that of ED. The oral bioavailability of EPBCN was 7.35 folds than that of ED. 90% confidence interval of area under concentration-time curve (AUC_{0-72 h}) and peak concentration (??_max) exceeded the standard range. CONCLUSION EPBCN can remarkably increase the release in vitro and oral bioavailability in rats, and they do not have bioequivalence.     

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??OBJECTIVE To investigate the enhancing effect of borneol on the absorption of chlorogenic acid (CGA) with two different biological models and to evaluate the correlation of these two models. METHODS The in situ rat perfusion model was used to investigate the enhancing effect of borneol on the absorption of CGA. The in vivo pharmacokinetics study was carried out to evaluate the correlation of the two-compartment open model.RESULTS With the in situ rat perfusion model, the absorption rate constant (Ka) of CGA was 0.083 4 h^-1,which was up to 1.58-fold higher by borneol. The results of in vivo pharmacokinetics study in rats suggested that 0.04% borneol could increase the relative bioavailability by 116.02% and maximum plasma concentration increased slightly. The consistent result of these two different absorption models was provided (r??0.941). CONCLUSION Borneol could promote the oral absorption of CGA.