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??OBJECTIVE To prepare the total alkaloids of Strychni Semen(TASS)-total glucosides of Paeony(TGP) gel and study its in vitro transdermal absorption of two alkaloids(strychnine and brucine) after the combination of TASS and TGP. METHODS The excised abdominal skin of mice was used as the permeation model. Utilizing the modified Franz diffusion cell, the suitable receiving solution was elected to test the content of two alkaloids by HPLC, and thus the percutaneous rates and permeability coefficients were obtained. RESULTS 20% Ethanol-normal saline was taken as receiving solution. With combination use of TASS and TGP, the penetration quantities of strychnine and brucine in different (1:1,1:3,1:6) gels were felled by 22.7%,48.4%,69.1% and 5.93%,23.8%,80.7% after 24 h. And with the increase of compatibility proportion, infiltration rate and skin retention rate also gradually reduced. CONCLUSION The compatibility of TASS and TGP drug delivery can reduce the toxic ingredients through capacity, there is a “attenuated” effect, the best ratio is 1:6.     

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??OBJECTIVE To investigate the contents of oligosaccharides in 37 batches of Morinda officinalis How samples from different habitats and germplasm resources at various ages. METHODS HPLC-ELSD method was used to determine the contents of four oligosaccharides, i.e sucrose, 1-kestose, nystose and 1^F-fructofuranosylnystose in Morinda officinalis How at different ages from different habitats and germplasm resources. The relationships among the several factors were analyzed. RESULTS The samples from Guangdong Province had larger amounts of sucrose, 1-kestose and 1^F-fructofuranosylnystose than those from Fujian, Guangxi and Hainan Provinces. The content of nystose in the samples from Guangdong Province was similar with those from Fujian Province. The contents of sucrose and 1-kestose were the highest in the samples of 2.5 years old, while the contents of nystose and 1^F-fructofuranosylnystose were the highest in the samples of 4 years old. The germplasm resources of small leaf had higher content of oligosaccharides than the large leaf germplasm in Guangdong Province, and different germplasm resources of Morinda officinalis How also had different morphological characteristics. CONCLUSION The contents of four Morinda officinalis How oligosaccharides vary with habitat, germplasm and age. This research may provide references for the quality control of Morinda officinalis How.     

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??OBJECTIVE To investigate the impacts of particle size and preferred orientation on relative peak intensity, number of peaks and order of peak intensity in powder X-ray diffraction (PXRD) analysis of organic and inorganic pharmaceutical crystalline materials and evaluate the phase identification methods in various pharmaceutical compendiums.METHODS The PXRD patterns of organic and inorganic materials with different particle sizes obtained by sieving or grinding were acquired and the number of diffraction peaks, peak position and intensity of diffraction peaks were compared across different samples. RESULTS Due to preferred orientation effects, the diffraction patterns of samples with different particle sizes were apparently different, including the number of peaks, relative peak intensity and the order of the peak intensity. CONCLUSION Scientists may get different CONCLUSION s from the RESULTS of same tests performed according to the related guiding principles of current Chinese Pharmacopeia and USP39, EP8.0, JP16 ???? pharmacopoeia for identifying the crystalline forms.The phase identification by PXRD method in current Chinese Pharmacopeia neglects the effects of preferred orientation on diffraction peaks and relative peak intensity. This guideline needs to be updated to better reflect the scientific observation in industry and align with other well accepted compendiums such as USP, EP and JP.     

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??OBJECTIVE To measure medication adherence to hypoglycemic drugs before admitted to hospital, assess the relationship between medication adherence and glycosylated hemoglobin (HbA1c) among inpatients with type 2 diabetes. METHODS The medication adherence of 415 cases of type 2 diabetes inpatients were investigated through MMAS-8(?i2006 Donald E. Morisky),the association between medication adherence and HbA1c was analyzed. RESULTS The mean medication adherence score was 6.18??1.99, 34.0% which was found to be good adherent. Medication adherence to hypoglycemic drugs were influenced by sex, age and chronic complications, which was also found to be correlated to HbA1c negatively (P=0.014). CONCLUSION Our RESULTS indicat that medication adherence to hypoglycemic treatment in our study is not optimal, the control condition of HbA1c is unsatisfactory. Medication adherence to hypoglycemic treatment is related with HbA1c, therefore, medication adherence could be a tool help to identify patients with poor blood glucose control.     

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??OBJECTIVE To develop an UPLC method for simultaneous determination of seven components in Gardenia jasminoides, ie, gardoside, shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside (RG), genipin-1-??-D-gentiobioside, chlorogenic acid, and gardenoside to evaluate the quality of Gardenia jasminoides. METHODS ACQUITY UPLC HSS T3 column was used for the UPLC analysis. The mobile phase was acetonitrile-0.05% phosphoric acid solution. Gradient elution was conducted at a flow rate of 0.2 mL??min^-1. The column temperature was maitained at 30 ?? and detection wavelength was set at 238 nm. A linear model was obtained through principal component analysis (PCA), and the scores of the principal components were used to evaluate the quality of Gardenia jasminoides Alba decoction pieces comprehensively. RESULTS The seven components could be well separated from each other with good specificity, precision,repeatability,linearity,recovery rate and stability.The 25 Gardenia jasminoides Ellis samples and two Gardenia jasminoides Ellis var.grandiflora Nakai samples conformed to the quality requirements in the chapter of gardoside, shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside(RG), genipin-1-??-D-gentiobioside, chlorogenic acid, gardenoside. As the comprehensive evaluation shown, the quality of wild Gardenia jasminoides samples from Jiangxi province was better; Gardenia jasminoides from inland provinces excelled those from coastal provinces; and Gardenia jasminoides across Jiangxi province were of stable and higher quality. CONCLUSION The method established in this study can effectively assay geniposide, gardoside, shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside and genipin gentiobioside in Gardenia jasminoides, thus it can be used for the quality control of Gardenia jasminoides.     

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??OBJECTIVE To standardize the concept and nature of food and drug regulatory filing behavior. METHODS According to the provisions of laws, regulations, rules and regulatory documents in the regulation of food and Drug Administration, analyze the existing problems and application defects in the regulation of food and drug regulatory record. RESULTS To suggest how to design and perfect the food and drug regulatory filing system. CONCLUSION As a widely applicable administrative act, administrative record is closely related to the administrative organ and the administrative relative person. Administrative filing as an extensive application, and administrative organs and administrative counterparts are closely related to the administrative behavior, more and more play an important role. Therefore, it is necessary to clean up those filing provisions, which are not standardized in the existing laws, regulations, regulations; to regulate the establishment of food and drug regulatory administrative record; to build a sound food and drug regulatory administrative filing procedures.     

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??OBJECTIVE To investigate the microbial contamination of trichosanthis fructus decoction pieces, and provide a reference for the test method and standard of the microbial limit. METHODS Trichosanthis fructus decoction pieces were tested for the total aerobe microbial count, the total combined yeasts and molds count, the thermoduric bacteria count, the bile-tolerant gram-negative bacteria, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella.RESULTS The total contamination percentages of aerobes, combined yeasts and molds, thermoduric bacteria, bile-tolerant gram-negative bacteria of trichosanthis fructus are 100%, 59%, 91%, and 91%,respectively. Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and salmonella of trichosanthis fructus were not detected.CONCLUSION To assure the safety of trichosanthis fructus decoction pieces, it is recommended to control the total aerobe microbial count, the total combined yeasts and molds count, the thermoduric bacteria count, the bile-tolerant gram-negative bacteria, escherichia coli, staphylococcus aureus,pseudomonas aeruginosa and salmonella.     

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??To improve the in vitro dissolution and in vivo absorption as well as the bioavailability after oral administration by increasing the solubility with the formation of solid dispersion remains a great challenge for the oral dosage form design of poorly water-soluble drugs. Compared with the other pharmaceutical techniques in improving the solubility for poorly water-soluble drugs, priorities are usually given to solid dispersion for its manufacturing convenience. Following the characteristics introduction, we were focused this review on the novel carriers and advanced techniques used for preparing solid dispersions. Amphiphilic polymers used as novel solid dispersion carriers are Solutol HS 15, Soluplus and poly [MPC-co-BMA]. Inorganic materials like magnesium aluminum metasilicat, mesoporous silica microparticle and mesoporous magnesium carbonate are introduced together with the advanced solid dispersing techniques such as supercritical fluid technology, high speed electro-spinning and microenvironmental pH modified technology.     

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??OBJECTIVE To study chemical constituents from the twigs and leaves of Illicius majus Hoot et Thoms. METHODS The compounds were isolated by column chromatography on silica gel, Sephadex LH-20, and flash chromatography coupled with preparative HPLC. Their structures were elucidated by spectroscopic analysis including IR, NMR, and MS. RESULTS Six compounds, ie. majusanicol(1), angustanoic acid G(2), 4-hydroxyphenethyl alcohol(3), 4-hydroxybenzoic acid(4), 3-hydroxybenzoic acid(5), and 3, 5-dimethoxy-4-hydroxybenzoic acid(6), were isolated from the twigs and leaves of I. majus. CONCLUSION Compound 1 is a new abietane-type diterpenoid, and compound 3-6 are isolated from this plant for the first time.     

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??OBJECTIVE To observe the effect and mechanism of Bauhinia championii flavones (BCF) on anti-hypoxia/reoxygenation injury in cardiomyocytes via inhibiting necroptosis. METHODS The cardiomyocytes hypoxia/reoxygenation injury model was developed and pretreated with Bauhinia championii flavones. ELISA was used to evaluate the contents of TNF-??, and the activities of T-AOC were determined by ultraviolet spectrophotometric method. The protein expression of RIPK3 was observed by Western-blotting, and the necroptosis rate was determined by using Annex v-FITC/PI double staining.RESULTS Compared with model group, Bauhinia championii flavones pretreatment alleviated cardiomyocytes injury, increased T-AOC level, decreased the activity of TNF-??, down-regulated the expression of RIPK3, and inhibited cardiomyocytes necroptosis(P<0.05). It had synergistic effect when combined BCF with necrostatin-1(P<0.05). CONCLUSION BCF can inhibit necroptosis and has protective effects on hypoxia/reoxygenation injury, which are associated with increasing the level of T-AOC, down-regulating TNF-?? and RIPK3, and decreasing the cardiomyocytes necroptosis rate.     

多糖放射性同位素标记及其体内药动学应用的研究进展

多糖具有良好的药理活性和较低的毒副作用,关于天然多糖药理活性的报道也是层出不穷。随着对多糖理化性质研究的进一步深入,多糖作为生物材料也逐渐用于新制剂的开发。但是相较于多糖药理活性和作为生物材料的研究,多糖体内药动学的研究十分匮乏,这严重限制了多糖进一步的开发应用。目前,体外放射性同位素标记成为了多糖体内药动学研究的重要手段,本研究总结了用于多糖标记的各种放射性同位素,并分析了不同放射性同位素在多糖体内药动学研究中的特点,以及影响多糖药动学的因素和基于多糖体内药动学特征的应用。对多糖体内药动学的深入研究,能够为多糖作为药品和生物材料的开发提供重要的指导。     

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??OBJECTIVE To investigage the effects of celastrol-triggered HeLa cells autophagy and the molecular mechanisms in vitro and in vivo. METHODS The antiproliferative effect of celastrol was detected using MTT assay. Apoptotic rate and cell cycle were evaluated using flow cytometric analysis. Autophagy was detected using fluorescence microscope. Protein expression was evaluated using Western blotting. Tumor growth was evaluated by subcutaneous xenograft model in vivo. RESULTS Celastrol inhibited HeLa cells proliferation and induced HeLa cells autophagy and cell cycle arrest at G₀/G₁ phase, but not induced HeLa cell apoptosis in vitro. The protein expression of Beclin 1 was up-regulated and the conversion from LC3 ?? to LC3 ?? was increase in HeLa cells in vitro after treatment with celastrol. Moreover, celastrol promoted the protein expression of PTEN??p-ERK1/2??p-MEK1/2 and inhibited the phosphorylated of Akt, p70S6K and mTOR in HeLa cells. After pretreatment with 3-methyladenine (5 mmol??L^-1), the antiproliferative and induced-autophagy effects of celastrol were reversed. Furthermore, celastrol inhibited tumor growth and the protein expression of p-Akt and p-mTOR, but up-regulated the protein expression of LC3 ?? and Beclin 1 in vivo. CONCLUSION Antitumor effect of celastrol dependent on cells autophagy in HeLa cells via inhibition of Akt/mTOR signaling pathway in vitro and in vivo.     

已公布的卡马西平片参比制剂在体内外的相关性研究

目的 以2家企业、2种规格的卡马西平片作为参比制剂进行体内外相关性研究,指导国内仿制药企业更好地开展仿制药一致性评价工作。方法 测定北京诺华和太阳药业(日本)生产的卡马西平片参比制剂在5种不同溶出介质中的溶出曲线,随后应用Gastro Plus软件建模、人工仿生膜结合Macro Flux^TM 型药物溶出度与渗透速率测试系统进行体内外相关性研究,预测2家参比制剂的体内生物等效性。结果 2家企业的卡马西平片参比制剂在5种溶出介质中的溶出曲线均不相似,Gastro Plus软件虚拟生物等效性(BE)与溶出-渗透测定结果显示2家制剂在空腹和饱腹2种状态中均存在生物不等效风险。结论 本研究发现2家企业的卡马西平片参比制剂体外溶出不一致,软件建模预测及人工仿生膜技术预测其体内存在生物不等效的风险,对同时生产两种规格制剂的企业而言,可能导致同一企业不同规格的仿制药在一致性评价中存在生物不等效的风险,建议国家药监局确定唯一企业的参比制剂。本研究为卡马西平片参比制剂的选择提供了数据基础,也为窄治疗窗口药物参比制剂的遴选和确定提供参考,同时为仿制药一致性评价提供技术支撑。     

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??PEGylated UOX is a kind of modified pharmaceuticals designed by coupling PEG with UOX to increase in vivo circulation half-life and reduce immunogenicity. UOX is modified by PEG at random multiple sites, which RESULTS in more complicated physical and chemical characteristics and in vivo and in vitro activities than UOX. At present, there is no standardized quality analysis method for such drugs. Through collecting and summarizing references about the quality control method of PEG-modified drugs in recent years, this article summarizes the analysis METHODS for three difficulties of the quality control of UOX namely the average extent of modification, consistency of modification and PEGylation sites so as to provide technical guidance for enterprises to develop the drug.     

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??OBJECTIVE To evaluate the anti-hepatitis B virus (HBV) activity of herpetrione nanosuspension (PEDX-NS) both in vitro and in vivo. METHODS HepG2 2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models were used to compare the anti-HBV activity of PEDX-NS and PEDX coarse suspension (PEDX-CS). RESULTS In the HepG2 2.2.15 cell, PEDX-NS effectively suppressed the secretion of the HBV antigens (HBsAg and HBeAg) in a dose-dependent manner with significant difference from PEDX-CS (P<0.05 or P<0.01). In the in vivo evaluation, PEDX-NS with high dose (100 mg??kg^-1) and middle dose (60 mg??kg^-1) significantly reduced the serum HBV DNA level (P<0.05 or P<0.01) and the effect was better than that of PEDX-CS (P<0.05 or P<0.01). CONCLUSION The result revealed that PEDX-NS exhibits anti-HBV activity both in vitro and in vivo and its effect was superior to that of PEDX-CS. The mechanism is probably that the small particle size of PEDX-NS provides a large specific surface area that resulted in better absorption in vivo, thus enhancing its anti-HBV activity.
     

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??With the continuously clinical study of capsaicin, capsaicin-drug interaction has become increasingly prominent. In recent years, the studies indicate that capsaicin shows a significant inducing or inhibitory effect on a variety of drug metabolism enzymes and transporters, thereby leading to the occurrence of complex drug interactions and affecting the other drugs in vivo process. In this paper, the modulation effect of capsaicin on drug metabolizing enzymes and transporters by reviewing the relevant research at home and abroad in recent years were summarized, and the drug-drug interactions associated with capsaicin in order to provide theoretical guidance for clinical rational drug use were explored . Furthermore, complex drug-drug interaction studies can be provided with prior examples.     

国产非那雄胺片与原研制剂体外溶出一致性评价及采用计算机模拟技术建立体内外相关性模型研究

目的 通过比较国产非那雄胺片与原研制剂的体外溶出行为,评价仿制药与参比制剂的质量一致性,利用计算机模拟技术分析体内外相关性。方法 参照《中国药典》2015年版方法(2020年版《中国药典》该项目没有变化),分别考察国产制剂与原研制剂在4种不同溶出介质(pH 1.2盐酸溶液、pH 4.5醋酸盐溶液、pH 6.8磷酸盐溶液、水)中的体外溶出行为。同时借助GastroPlus^TM软件结合体外溶出试验结果,建立非那雄胺片体内外相关性模型。结果 在选定条件下,国内15家制药公司中有3家公司产品在4种溶出介质中的溶出曲线均与原研制剂相似。软件分析结果提示,体外溶出曲线与软件模拟的体内行为不相似。结论 大部分非那雄胺片仿制制剂在体外的溶出曲线与原研制剂存在一定的差异,国产非那雄胺片工艺水平及处方有待提高,反映体内释放行为的生物体相关溶出条件有待进一步研究。     

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??OBJECTIVE To study the hepatotoxicity of Polygonum multiflorum on the basic of the bilirubin metabolism mediated by glucuronidation of UGT1A1 enzyme. METHODS Inspected the enzyme kinetic parameters after giving the rats Polygonum multiflorum extract orally(in vivo), and added the Polygonum multiflorum extract into the human liver microsome(rat liver microsome; human recombinant UGT1A1 enzyme) to test the hepatotoxicity using the bilirubin as UGT1A1 enzyme substrate, investigating the inhibition of the UGT1A1 enzyme(in vitro). Apparent inhibition constant K_i and enzyme kinetic parameters were used to evaluate the hepatotoxicity. RESULTS Polygonum multiflorum extract has a strong inhibiton to the UGT1A1 enzyme in all the three systems in vitro. All the type of inhibition is the competitive inhibition. While Polygonum multiflorum extract has a strong inhibiton to the UGT1A1 enzyme in vivo, but the type of inhibition is the uncompetitive inhibition.CONCLUSION The method we had established in our study provides a new idea and a new method to evaluate the hepatotoxicity and the safety of Chinese herbs.     

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??To summarize the research progress of the regulation of lipid metabolism by citrus flavonoids. Recent research articles were analyzed and summarized. Citrus flavonoids are mainly flavanones and polymethoxyflavones, and they can regulate lipid metabolism and prevent atherosclerosis in vitro and in vivo. Factors such as different flavonoid profiles, dosage, time, and experimental models all affect the effectiveness. Citrus flavonoids have great application potentials in regulation of lipid metabolism in vivo, and it has both theoretical and practical significance to screen and study citrus flavonoids.     

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??OBJECTIVE To establish a measuring method for microdialysis probe recovery of ginsenoside Rg₁ and investigate the effects of flow rate, concentration and using times of probe on the recovery in vivo and in vitro. METHODS Dialysis method and retrodialysis method were used for the study. The concentration of ginsenoside Rg₁ in brain and blood dialysate was determined by LC-MS/MS and the probe recovery was calculated. RESULTS The recoveries of brain and blood microdialysis probes showed good stability within 10 h, with average values of 17.0% and 34.4% respectively for ginsenoside Rg₁ at 1.5 ??L??min^-1. Concentrations (50,200,500,1 000 ng??mL^-1) had no obvious effect on recovery. At the same concentration, the recovery of brain and blood probes for ginsenoside Rg₁ decreased with the increase of flow rate (0.5, 1.0, 1.5, 2.0, 3.0 ??L??min^-1) in vitro and in vivo. The dialysis recoveries of brain and blood probes in vitro were (40.6??4.3)%, (23.5??2.3)%, (17.7??0.8)%, (12.2??1.1)%, (8.8??0.6)% and (70.6??3.6)%, (46.0??2.1)%, (32.9??1.6)%, (25.6??0.7)%, (18.2??1.3)%, respectively. The recoveries of dialysis and retrodialysis in vitro were approximately equal, and the recovery detected by retrodialysis in vivo was similar with the in vitro results. Probe used for no more than 3 times still kept high transmittance by flushing with 2% heparin sodium and ultrapure water successively. CONCLUSION Retrodialysis method can be used to study brain and blood probe recovery in vivo, and microdialysis can be used for simutaneous pharmacokinetic studies of ginsenoside Rg₁ in intercelluar fluid and blood.