With high internal and external surface area and pore volume,adjustable pore size,colloidal stability,favorable biocompatibility,diverse surface chemistry,scientists in nanomedicine field pay intensive attention on porous silica spheres.In this review,at first,the fabrication strategy of porous silica spheres with different structure,such ashierarchical solid sphere,core shell spheres and porous hollow spheres was discussed;then explore the various responsive strategy used for controllable drug delivery system;and lastly review the application of porous silica carriers in controlled drug delivery.
Transdermal drug delivery is advantageous over oral medication or injection,as it can circumvent the first pass effect and increase bioavailability.Located within skin,a series of transporters affect the transdermal delivery of therapeutic molecules.Therefore,it is important to study the distribution and functions of these transporters in pharmaceutical and cosmetic applications.The transporters can be categorized into two major groups,the ATP-binding cassette (ABC) transporters and the solute carriers (SLC),both of which are found in skin and can affect drug permeation.In this review,the transporters in skin and their roles for transdermal drug delivery were summarized and discussed.
Objective To investigate the effect of nicotine and cannabinoids on synaptic plasticity in the VTA dopamine neuron, and to explore the neuromechanism of drug addiction and to provide candidate therapeutic strategy for treating drug addiction. Methods Two-month old SD rats were randomly and equally divided into 4 groups:control group, HU210 group, nicotine group, and nicotine+HU210 group.The HU210 group received HU210 (100 μg·kg-1,intraperitoneal injection) once a day for 5 days.The nicotine group received nicotine (0.5 mg·kg-1, hypodermic injection) once a day for 5 days.The HU210+ nicotine group received HU210 (100 μg·kg-1, intraperitoneal injection) and nicotine (0.5 mg·kg-1, hypodermic injection) once a day for 5 days.Control group received vehicle intraperitoneal injection and hypodermic injection once a day for 5 days.High-frequency stimulation (HFS) or low-frequency stimulation (LFS) was given to induce long-term potentiation (LTP) or long-term depression (LTD) in VTA of each group 24 h after last injection, then field EPSPs (fEPSPs) was recorded. Results It has been shown that LFS of VTA local excitatory afferents induced LTD after chronic injection (once daily injections for 5 days) of HU210, while HFS could not induce LTP.HFS of VTA local excitatory afferents induced LTP after chronic injection (once daily injections for 5 days) of nicotine, while LFS could not induce LTD.Daily chronic injection of nicotine and HU210 together prevented HFS-induced VTA LTP and LFS-induced VTA LTD. Conclusion Chronic injection of HU210 induces LTD and chronic injection of nicotine induces LTP.LTD and LTP can be neutralized after co-administration of HU210 and nicotine in VTA.
Objective To investigate the effects of CQMUH-011 on proliferation and phagocytosis of macrophages. Methods MTT assay was used for detecting the effects of different concentrations of CQMUH-011 pretreatment for different time on the proliferation of macrophages (RAW264.7) induced by lipopolysaccharide (LPS).Enzyme-linked immunosorbent assay (ELISA) was used for examining the effects of CQMUH-0011 on the secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induced by LPS.Carbon clearance experiment and peritoneal macrophages phagocytosis experiments were used for detecting the effects of CQMUH-011 on phagocytosis of macrophages in mice. Results The most significant inhibitory effect of CQMUH-011 on the proliferation of LPS-induced RAW264.7 cells was at the concentration of 1 μmol·mL-1 and pretreatment for 24 h (P<0.01), and the levels of inflammatory cytokines such as TNF-α and IL-1β induced by LPS at different time points were significantly inhibited (P<0.01).Moreover, 225 μg·kg-1 of CQMUH-011 significantly inhibited the carbon clearance rate and phagocytosis of macrophages (P<0.01). Conclusion CQMUH-011 inhibits the proliferation, inflammatory factor production and phagocytosis of macrophages.
Objective To study the effect of Naosuikang on the cognitive function of vascular dementia (VaD) rats. Methods Male Sprague-Dawley rats were randomly divided into two groups according to the randomized block method.The VaD models were established by bilateral carotid artery ligation and randomly divided into model control group, sham operation group,donepezine hydrochloride group, and Naosuikang low,medium and high dose groups.The model control group and sham group were given intragastric administration of 0.9% sodium chloride solution 10 mL·kg-1·d-1;the donepezil hydrochloride group was intragastrically administered with donepezil hydrochloride 0.52 mg·kg-1·d-1,Naosuikang high,medium and small dose groups were fed with 31.04, 15.52 and 7.76 g·kg-1·d-1 Naosuikang,respectively.After 6 weeks of dosing,the Morris water maze test was used to evaluate the effect of Naosuikang on the cognitive function of VaD rats by evasion latency,total swimming distance,and number of crossing platform. Results Compared with the model control group,the escape latency and the total swimming distance were significantly shortened (P<0.01) in the Naosuikang low,middle,and high dose groups.Compared with the model control group,number of crossing platform was significantly increased in the donepezil hydrochloride group and the Naosuikang high, medium and small dose groups (P<0.01). Conclusion Naosuikang can obviously improve the cognitive function of VaD rats.
Objective To study effect of different doses of Zhengan xifeng decoction on vascular tissue morphology of aortic arch in spontaneously hypertensive rats (SHR). Methods A total of 50 male SHR,24 weeks old,were randomly divided into model control group,low,medium,high dose of Zhengan xifeng decoction groups and compound apocynum group,10 in each group.Ten homologous male rats (WKY) served as normal control group.The model control group and normal control group were fed with 4 mL·d-1 0.9%sodium chloride solution.Low, midium and high dose groups were fed with Zhengan xifeng decoction (13.5,27,54 g·kg-1·d-1,respectively).Compound apocynum group was fed with 54 g·kg-1·d-1 compound apocynum suspension.After 50 days,the histopathological changes of the aortic arch were observed with HE staining. Results Compared with the model control group,the wall diameter of the aortic arch was significantly reduced in the middle dose group,high dose group,and compound apocynum group (P<0.01).There were no significant difference in the wall diameter of the aortic arch between the high dose group,the compound apocynum group and the normal control group (P>0.05).There was no significant difference in the wall diameter of the aortic arch between the high dose group and the compound apocynum group (P>0.05). Conclusion Zhengan xifeng decoction can improve the pathological structure of SHR vascular wall,reduce the injury of blood pressure to vessel wall,and reduce the thickening of vessel wall.
Objective To discuss the effect and mechanism of bevacizumab (BEVA) combined with photothermal therapy (PTT) in inhibiting metastatic tumor. Methods Balb/c mice were inoculated in the lateral flank with 4T1 cells and randomly divided into three groups:PTT group,PTT + BEVA group,and the control group.Intraperitoneal injection of BEVA (7.5 g·kg-1,three times in total) and combined therapy with PTT were given according to schedule respectively.Five days after PTT,mice were injected with 4T1-luc cells through the tail vein to simulate tumor metastasis.The lung tumor load of each group was observed through the small animal in vivo imaging system (IVIS).Part of the mice were sacrificed three days after PTT,the tumor draining lymph nodes of these mice were collected and analyzed by a flow cytometry in order to detect the maturation state of dendritic cells (DC). Results Results showed that the combined treatment of PTT and BEVA partially inhibited the metastatic tumor in the lung.Flow cytometry results showed that the DC activation in tumor draining lymph nodes in the combined treatment group was significantly higher than that in the control group. Conclusion Combined treatment of PTT and BEVA may inhibit tumor metastasis and tumor recurrence through promoting maturation of DC in lymph gland,increasing anti-tumor immune response stimulated by PTT, by exerting synergistic effect.
Objective To study the effect of edaravone on chronic obstructive pulmonary disease (COPD) in rats and the possible mechanism. Methods Healthy male SD rats were randomly divided into blank control group, model control group,N-acetylcysteine group,edaravone low,middle and high dose groups (Eda1,Eda2,Eda3 groups).Except for the blank control group,rats of each group were administered with intratracheal instillation of lipopolysaccharide and exposed to cigarette smoke to establish COPD mode.The rats in NAC group,Eda1 group,Eda2 group and Eda3 group was intraperitoneally injected with 20 mg·kg-1 NAC, 10 mg·kg-1 Eda, 20 mg·kg-1 Eda, 40 mg·kg-1 Eda, respectively, before exposure to cigarette smoke.The rats in model control group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution before exposure to cigarette smoke.The rats in blank control group were not exposed to cigarette smoke, same amount of 0.9% sodium chloride solution was intratracheally instilled and intraperitoneally injected.After four weeks, the lung function and the level of malondialdehyde and superoxide dismutase in plasma were measured.The levels of tumor necrosis factor-α and interleukin-8 in the supernatant of bronchoalveolar lavage fluid were measured.The expression of matrix metalloproteinase (MMP-9,MMP-12) and tissue inhibitor of metalloproteinase-1 were detected by immunohistochemistry. Results As compared with the blank control group, the levels of MDA, SOD, TNF-α and the expression of MMP-9, MMP-12 and TIMP-1, and the ratio of MMP-9/TIMP-1 and MMP-12/TIMP-1 were significantly increased in model control group (P<0.05).Compared with model control group, NAC and medium and high dose of edaravone could significantly decrease the levels of MDA and the expression of MMP-9, MMP-12 and TIMP-1 in rat plasma and the ratio of MMP-9/TIMP-1 and MMP-12/TIMP-1 (P<0.05).NAC could significantly inhibit the increase of SOD activity (P<0.05).NAC and all doses of edaravone could decrease the level of TNF-α in BALF of rats (P<0.05). Conclusion Edaravone can exert anti-COPD effect by antioxidant,inhibiting the infiltration of inflammatory cell and releasing inflammatory factors,and balancing protease/anti-protease expression.
Green therapy of tumor, being different from traditional treatment mode, aims at keeping patients’living quality.The principle of treatment is control rather than cure.Under the guidance of TCM and Chinese philosophy,the treatment includes minimally invasive surgery,traditional Chinese medicine,immunotherapy,low dose radiotherapy and chemotherapy, and all of the treatment methods are in accordant with “low in damage and sustainable” principle,It can be called Chinese anti-cancer principle which has continuity and repeatability.
The concept of "tumor green therapy" believes that the occurrence of tumors is closely related to the "cancerism",Therefore, changing the patient's constitution is particularly important in the treatment of cancer. Professor Hu Kaiwen improved patients cancerism mainly through these aspects:①Strengthening and enforcing Zheng Qi;②Leading Fire to Its Origin;③Coordinating qi movement;④The application of insect drugs;⑤Reasonable using the external treatment of TCM。Based on the concept of tumor green therapy, this article summarizes the experience of using "tumor green therapy" to improve the constitution in treating malignant tumors.
In this study, we summarized the understanding of traditional Chinese medicine (TCM) on the etiology and pathogenesis of malignant tumors,and used Yueju pills as a basic prescription for addition and subtraction to prevent and treat malignant tumors from “theories,methods,prescriptions,and medicines”.We also discussed the correlation between the tumor micro-environment and TCM pathological factors of malignancy.Moreover, the feasibility of using Yueju pills as a basic prescription for addition and subtraction to treat malignant tumors was evaluated according to the pharmacology of TCM.
The mode of “green therapy of cancer” divides the treatment of tumor into three stages:“hegemony” “king” and “emperor”.In emperor way,they emphasize that the TCM therapy for tumor should combine integral syndrome differentiation and local syndrome differentiation, attacking pathoge and invigoration, syndrome differentiation and disease differentiation, usually using “Yinhuo decoction” which can bring significant treatment effect as a base to add and subtract.The Yinhuo decoction,designed by professor Hu Kaiwen after combining his own years of clinical experience, includes prepared rehmannia root 90 g,morinda officinalis 30 g,poria cocos 15 g as a component.The Yinhuo decoction which is in principle of tonifying Yin and Yang and guiding fire to origin brings a good antidote to patients with the deficiency of Yin and Yang and the constitution of heat in the upper and cold in the lower,providing a new idea for improving the internal environment of tumor patients.
Objective Under the guidance of the theory of “Tumor Green Therapy”,to observe the curative effect and adverse reactions of umbilical therapy with Shengxuefang for cancer related anemia of erythropoietin. Methods A total of 90 patients with cancer related anemia of erythropoietin antagonism were randomly divided into blank group, moxibustion group and umbilical therapy group.All patients were treated for 14 days.Blood routine and of symptoms score for EORTC-QLQ-C30 were observed. Results Compared with blank group,the hemoglobin level of moxibustion group and umbilical therapy group increased significantly (P<0.05),while the effect of umbilical therapy group was more significant (P<0.05).Umbilical therapy group could also significantly reduce the symptom scores of fatigue and appetite loss (P<0.05). Conclusion Moxibustion therapy has a certain effect on improving erythropoietin antagonistic anemia,but it was better in combination with Shengxuefang umbilical therapy,it was more secure and could improve symptoms of fatigue and appetite.
Objective To investigate the effect of adefovir dipivoxil and entecavir separately combined with pegylated interferon on serum parameters,ALT normalization rate and adverse reactions of patients with resistant e-antigen positive hepatitis B. Methods Totally,100 patients with resistant e-antigen positive hepatitis B were randomly divided into group A (50 patients,treated with adefovir dipivoxil combined with pegylated interferon and group B (50 patients,treated with entecavir combined with pegylated interferon); The complete viral response rate,HBeAg negative conversion rate,HBeAg transfer rate,DNA HBV negative conversion rate,HBsAg negative conversion rate,ALT normalization rate and adverse reaction incidence of both groups were compared. Results There was no significant difference in the complete viral response rate 24,48 and 72 weeks after the treatment between the two groups (P>0.05).The HBeAg negative conversion rate 24,48 and 72 weeks after the treatment were significantly higher in group B than in group A (P<0.05).There were no significant differences in the HBeAg negative conversion rate,DNA HBV negative conversion rate and HBsAg negative conversion rate after the treatment between the two groups (P>0.05).There was no significant difference in the ALT normalization rate 24,48 and 72 weeks after the treatment between the two groups (P>0.05).There was no significant difference in the adverse reaction incidence between the two groups (P>0.05). Conclusion Compared with adefovir dipivoxil,entecavir combined with pegylated interferon can efficiently increase the HBeAg seroconversion rate,improve the overall clinical efficacy,but not increase the adverse reaction risk in patients with resistant e-antigen positive hepatitis B.
Acidic fibroblast growth factor (aFGF), which is isolated and purified as the second member of fibroblast growth factor family.Because of its extensive physiological function, such as promoting wound healing,angiogenesis,nerve tissue nutrition and repair, it has attracted close attention.Nonetheless, the short half-life and easy degradation of aFGF limits the clinical application.In order to improve the hydrolysis and instability of aFGF, the study on aFGF controlled-release preparation through a good biological material carrier has become a research focus recently.Herein, we reviewed and discussed the several related biological material carrier experiments and application, and summarized the advantages, limitations and trends of progress.
Objective To establish a high performance liquid chromatography (HPLC) method for the determination of lysine hydrochloride in compound lysine granules. Methods The determination was performed on NH2 column (150 mm×4.6 mm,5 μm) with mobile phase consisted of 0.05 mol·L-1 ammonium dihydrogen phosphate at a flow rate of 0.5 mL·min-1.The column temperature was 25 ℃,and the detection wavelength was set at 205 nm. Results The linear range of them was 0.063-2.521 mg·mL-1(R2=1.000).The average recovery (n=9) was 99.2%. Conclusion The method is simple and accurate,and can be used for assay of lysine in compound lysine granules.
Objective To analyze the potential source of aluminum in compound amino acid injection according to the Good Manufacturing Practice (GMP) and drug production process. Methods Compound amino acid injection (20AA) was chosen as a simulated solution for analysis.It has the most comprehensive varieties of amino acids and the concentration of amino acids is 10%.More stringent conditions than the production process was used to carry out extraction test for activated carbon, which might be used in the production process, and packaging materials from different manufacturers.Aluminum content was measured by atomic absorption spectrophotometer. Results There were only a small number of dissolved aluminum ions from activated carbon, infusion bottles made of middle borosilicate glass, and halogenated butyl rubber stopper for injection, but aluminum ions dissolved from the infusion bottle made of soda lime glass were obvious. Conclusion In order to ensure clinical medication safety, the CFDA or other national drug regulatory authority should issue related regulation(s) on aluminum hazard from Compound Amino Acid Injection(s) as soon as possible.The drug manufacturers should focus on aluminum dissolution risk from packaging materials, stipulate the aluminum content detection in the drugs’ quality standard, and increase the warning content in the medicine specification about the aluminum risk.
Objective To study extraction technique of orientin-2″-O-β-L-galactopyranosylide (OGA) and total flavonoids from Trollius altaicus. Methods Based on the determination of OGA and total flavonoids content as well as evaluation of antioxidant activities, the extraction of flavone from T.altaicus was optimized by orthogonal experiment with these indexes.The ethanol concentration,solid to liquid ratio,extraction time and frequency were selected as affecting factors.Extraction technique of orientin-2″-O-β-L-galactopyranosylide (OGA) and total flavonoids from Trollius altaicus was optimized by L9(34) orthogonal experimental design. Results The optimum extraction technique was shown as follows:the ethanol concentration 70%,solid-liquid ratio 1:30 (g·mL-1) and the extraction time 1.5 h,frequency 2 times.The content of OGA and total flavonoids from T altaicus were (29.02±0.46)mg·g-1 and (170.53±3.30)mg·g-1 respectively under the optimal condition.The antioxidant activities were improved with the increase of total flavonoids and OGA contents in the extracts. Conclusion The optimum extraction process is suitable for industrial production due to its simple manipulation, and it can provide essential data for the development and utilization of T.altaicus.
Objective To explore the effects of different packaging materials on the contents of menthol and camphor in compound menthol nasal drops. Methods Menthol and camphor were determined by GC with heavy-gauge HP-FFAP capillary column as chromatographic column.The contents change of the two components in nasal drops of low density polyethylene (LDPE), polypropylene (PP), polyester (PET) and glass were investigated under the same storage condition. Results Contents of the two components in the preparation were decreased with time in 4 different packaging materials. Conclusion Different packaging materials have some effects on contents of the two components.It is preliminarily determined that PP was more suitable for menthol nasal drops.
Objective To optimize prescription of the floating tablet of pantoprazole sodium. Methods The tablets were prepared with direct compression method using hydroxypropyl methyl cellulose (HPMC) as matrix material.Specification and dosage of HPMC and types of fillers were investigated to study their influence on drug release.Indicated by in vitro release,formulation of pantoprazole sodium gastric floating tablet was optimized by orthogonal test. Results The in vitro release almost had no relevance to the specification of HPMC but related to dosage of HPMC and type of fillers.The optimized formulation was pantoprazole sodium 44 mg, HPMC (K4M) 120 mg, lactose 50 mg and magnesium stearate 2 mg.The 12 h accumulative release was more than 95% according to Higuchi equation (Q=31.278t1/2-12.444,r=0.999 4). Conclusion The pantoprazole sodium gastric floating tablet with optimized formulation shows good ability on floating and controlled releasing without delayed or sudden release.
Objective To establish a high performance liquid chromatography (HPLC) method for the determination of tenacissoside G in Marsdenia tenacissima (Roxb.). Methods Symmetry C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.1% phosphoric water (45:55), the flow rate was 1 mL·min-1,and the detection wavelength was 230 nm. Results The calibration curve of tenacissoside G was linear in the range of 4-80 μg·mL-1.The average recoveries of low,medium and high concentrations were 98.4%,99.3% and 98.8%,respectively;RSD were 0.29%,0.29% and 0.12%,respectively. Conclusion The established method was accurate,simple and reliable,and can be used for the quality control of Marsdenia tenacissima (Roxb.)
Objective To establish an HPLC analytical method for determining the genotoxic impurity isopropyl toluene-4-sulphonate in brinzolamide. Methods The method was performed on an Inertisl ODS-3 C18 (4.6 mm×250 mm,5 μm) column.The mobile phase was buffer (1.0 mL phosphoric acid and 1 000 mL water, pH adjusted to 3.0 with triethylamine)- acetonitrile (70:30) and the flow rate was 1.0 mL·min-1.The column temperature was 30 ℃.20 μL sample solution was injected into the HPLC system and the detection wavelength was 220 nm. Results The other impurities in brinzolamide did not interfere with the determination of isopropyl toluene-4-sulphonate,which had good specificity.The limit of detection was 0.008 5 μg·mL-1,and the limit of quantification was 0.028 4 μg·mL-1.The calibration curve of isopropyl toluene-4-sulphonate was in a good linearity over the range of 0.028 4-1.354 μg·mL-1(r=0.999).Determination repetition of isopropyl toluene-4-sulphonate was fine and RSD was 0.66% (n=6).The average recovery of isopropyl toluene-4-sulphonate was 96.9% and RSD was 0.70% (n=9). Conclusion The method was easy to operate,with acceptable accuracy and specificity,and applicable for the determination of genotoxic impurity isopropyl toluene-4-sulphonate in brinzolamide.
Objective To establish a method for the simultaneous determination of polydatin,resveratrol,naringin,neohesperidin,emodin and physcion in Qiguanyan syrup. Methods HPLC method was used.The separation was performed on the column of Inertsil ODS-SP C18 with mobile phase of acetonitrile-0.1% phosphoric acid solution (gradient elution) at a flow rate of 1.0 mL·min-1,the detection wavelength were set at 306 nm (polydatin,resveratrol) and 280 nm (naringin, neohesperidin,emodin and physcion),column temperature was 30 ℃,and the injection volume was 5 μL. Results The linear range was 36.32-726.4 μg·mL-1 (r=0.999 4) for polydatin,2.338-46.75 μg·mL-1 (r=0.999 9) for resveratrol, 4.147-82.94 μg·mL-1 (r=0.999 9) for naringin,5.310-106.2 μg·mL-1 (r=0.999 9) for neohesperidin,1.602-32.03 μg·mL-1 (r=0.999 9) for emodin,0.102 5-2.050 μg·mL-1 (r=0.999 9) for physcion.RSDs of precision, stability and reproducibility tests were less than 2.0%. The average recoveries were 97.2%(RSD=1.1%),96.0% (RSD=1.0%), 97.8% (RSD=1.6%),96.2% (RSD=0.8%),101.6% (RSD=1.8%) and 100.8% (RSD=1.9%) respectively. Conclusion The method was sensitive, accurate and reliable,and can be used for the simultaneous determination of six ingredients in Qiguanyan syrup.
In the USA, in order to speed up orphan drugs marketing, pharmaceutical enterprises apply for the grants of orphan drug research and adopt the accelerated procedure of the clinical trials for orphan drugs.And in order to increase the investment returns, the companies practice the market monopoly policy for orphan drugs, and use high pricing strategy and sale channel of specialty pharmacy and off-label use of orphan drugs, etc.The experience of the USA provides a useful reference for the establishment of the incentive mechanism and the positive development of orphan drug accessibility.However, the off-label sales of orphan drugs in China need to be cautiously conducted.