Objective: To study the characteristics and mechanism of transdermal delivery of sinomenine hydrochloride (SH) through mouse skin treated by solid silicon microneedle arrays. Methods: The amount of SH was determined by HPLC system. Hairless rat skin was pretreated with microneedle arrays. The side-by-side diffusion cell method was used to investigate the effects of needlepoint shape, different insertion forces, retention time, and number of microneedles on transdermal SH delivery. Skin samples treated by microneedles were made into paraffin sections for histological examination and were viewed by brightfield microscopy. Results: The skin pretreated with microneedle arrays had a remarkable enhancement of SH transport compared with passive diffusion group (P<0.01); the flat tipped microneedles were more effective than the sharp tipped microneedles in enhancing the skin permeability. The accumulation of SH increased with the enhancement of insertion force; however, when the insertion force exceeded 5.0 N, the accumulation of SH no longer increased. The skin permeability was enhanced with the increase of retention time; when the retention time exceeded 1.0 min, it no longer increased SH accumulation. Although skin permeability increased with the microneedle number, there was no linear correlation was found. Histological examination showed that microneedle piercing created micro-conduits in skin. Conclusion: Microneedles can create conduits in rat skin and greatly increase the skin permeability of SH; microneedle arrays provide an efficient and promising technology for transdermal drug delivery of SH.

Acute Disease ; Adult ; Benzene ; poisoning ; Humans ; Male ; Multiple Organ Failure ; chemically induced ; Occupational Diseases ; complications

Objective: Through the studies on pilot production of the cataplasma of Chinese materia medica (CMM) containing volatile oil, to provide a rational and feasible preparation technology for the pilot production of CMM cataplasma, so as to promote the development of CMM cataplasma. Methods: The CMM containing volatile oil was extracted by steam distillation method (SDM), ethanol reflux extraction (ERE), and CO2 supercritical fluid extraction (SFE), respectively. The extracts were prepared to cataplasma in order to investigate the effects of extracting methods on the preparation process and quality of CMM cataplasma. The effects of micellar solubilization in the distilled liquid of STM on the quality of cataplasma such as adhesiveness, flexibleness, and stability were also investigated. Results: There was the significant difference among the groups of STM, ERE, and SFE on the quality of cataplasma. The extract by STM was beneficial to the preparation process and enhancement of the quality of cataplasma obviously, while the distilled liquid by STM would cause some limitations such as oil-water separation and volatile oil volatilization losses, which could contribute to obvious difference among batches. These disadvantages by STM would be overcome by the adoption of micellar solubilization technology and the stability would be increased (P < 0.01); segregation happened for the extract by ERE at room temperature, thereby, the water bath heating was needed in the preparation; this characteristics would cause the homogeneous appearance of cataplasma due to some black spots, lower flexibleness of matrix, and the preparation was not easy to control; the extract by SFE contained a lot of impurity of grease and performed half solid. As a result, it was very difficult to blend the extract by SFE with other materials uniformly, the adhesive force of cataplasma was also reduced. In addition, the cost of higher energy consumption and production was another disadvantage for SFE. Conclusion: The STM followed by micellar solubilization would be a feasible preparation technology for the pilot production of CMM cataplasma containing volatile oil, so it is worth popularizing and applying widely.

Objective: To reduce or avoid the volatilization loss of camphor (CA) in the industrialized preparation of cataplasm, using the inclusion technology of HP-β-CD. Methods: The HP-β-CD inclusion compound of CA (CA-HP-β-CD) was prepared by the constant temperature stirring method. The preparation processing of CA-HP-β-CD was optimized with inclusion efficiency as an index, and the pharmaceutical properties of CA-HP-β-CD were characterized by DSC, UV and SEM. The CA and CA-HP-β-CD were prepared to cataplasm at the industrial-scale production respectively, then the content of CA was determined and the statistical analysis was carried out. Results: The inclusion efficiency of CA-HP-β-CD for CA was (68.57 ± 1.26)% when the CA-HP-β-CD was prepared with the mass ratio of CA to HP-β-CD 1:3, the working temperature at 35 ℃ and stirring at 300 r/min for 4.0 h. The DSC, UV and SEM scans showed that there was a good compatibility between CA and HP-β-CD, and CA could be fully encapsulated by HP-β-CD and formed a stable inclusion complex of CA-HP-β-CD. Results of industrial-scale production of cataplasm for CA and CA-HP-β-CD revealed that the retention rate (actual content/feeding quantity) were (80.13 ± 1.05)% and (39.45 ± 1.38)%, respectively. And there was a statistically significant difference between them (t-test, P < 0.01), indicating that the HP-β-CD inclusion complex effectively reduce the volatilization loss of camphor CA. Conclusion: The volatilization loss of CA at the industrial-scale production of cataplasm was effectively reduced by the CA-HP-β-CD, which improves the utilization rate of CA and reduces the cost, and provides ideas and reference for the research and development of cataplasm of volatile drugs.

Objective:To obtain the optimal conditions for separating catalpol from leaves of Rehmannia by selecting appropriate macroporous adsorption resins.Methods:The detection indication was the content of catalpol, which was determined by HPLC method. Twelve different kinds of macroporous adsorption resins were studied on the static capacity of adsorption and desorption, and H103 resin was selected for the research of separation and purification.Results:The H103 resin had a good capacity for adsorption and desorption.The best process of purifying catalpol by H103 resin was 1mg/ml concentration, the adsorption rate of 1-2 BV/h,the flow rate of 1-3 BV/h, and 8 BV with 10% alcohol.Conclusion:The method is simple and available, which can simplify the production process and lower costs.

OBJECTIVE: To prepare palmatine-loaded flexible nano-liposomes (PFNL) and study their pharmaceutical properties, in order to lay the foundation for the industral application. METHODS: The flexible nano-liposomes were prepared by thin-film homogenization method with propyleneglycol (PG) as softening agent. The entrapment rate of palmatine was evaluated by protamine aggregation method and HPLC. The effects of concentrations of phosphatidylcholine (PSC), cholesterol (CH), and PG on the entrapment efficiency of palmatine were also investigated. The pharmaceutical properties of PFNL were evaluated by TEM, PCS and CLSM. The deformation of PFNL was determined by its relative rate of permeating the microporous filter membrane. The coagulation rate constant (K) was measured by constant temperature conductivity method. The side-by-side diffusion cells and pig vaginal mucosa were used to investigate the characteristics of the release of palmatine from PFNL in vitro, and the effects of PFNL on the expression of cytokines (SLPI, LF and SP-D) were investigated and compared with classic liposomes and lotion of palmatine. RESULTS: The palmatine entrapment efficiency was (78 ±2.13)% when the PFNL were prepared with PSC (3%), CH (0.02%), and PG (20%). The prepared nano flexible liposomes had a closed spherical or elliptical shape and appeared as multi-lamellar vesicles under the TEM and CLSM. The calculated mean size was (185 ±19) nm, and the Zeta potential was (-53 ±2.27) mV. The deformation of PFNL was (79 ± 5.75)%. The coagulation rate constant (K) of PFNL was always lower than that of traditional palmatine- loaded liposomes. The accumulated permeation amount of palmatine from the PFNL at 6.0 h was 1.53 and 2.86 folds of those of classic liposomes and lotion, respectively. Moreover, the expressions of cytokines (SLPI, LF and SP-D) in female SD rats after being treated with PFNL, PCL and PL were similar to that of the control group. CONCLUSION: The prepared PFNL have high encapsulation efficiency, good stability and safety, and greatly increase the vaginal mucosa permeability of palmatine. Flexible nano-liposomes may be a useful drug delivery carrier for the gynecological application of palmatine.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. However, due to its complex pathogenesis, there are no officially approved drugs for NAFLD treatment currently. Therefore, it is extremely urgent to find safe and effective anti-NAFLD drugs. Nowadays, lipid-lowering drugs are the main option for NAFLD therapy, but the clinical efficacy of chemical drugs is also very limited, as well as the frequent side effects or adverse reactions. Traditional Chinese medicine (TCM) has attracted more and more attention in the treatment of NAFLD due to its unique advantages through multiple targets and pathways with few side effects. In recent years, numerous studies have demonstrated that the imbalance of gut microbiota plays an important role in the occurrence and development of NAFLD. This review systematically summarizes the experimental and clinical evidences of TCM active compounds and TCM prescription involved in the regulation of intestinal flora in the treatment of NAFLD in recent years, so as to provide a reference for further exploring the pathogenesis of NAFLD and exploring TCM treatment methods.

Objective To investigate the effect of integrin-linked kinase (ILK) on inducing mesenchymal stem cells (MSCs) to neuron stem-like cell in vitro. Methods MSCs isolated from umbilical cord were transfected with plasmid DNA encoding green fluorescent protein (GFP) and GFP-fusion ILK, wild and mutant, respectively; and cultured in serum-free media with basic fibroblast growth factor, epidermal growth factor and B27. It was assessed with the proliferative activity and the efficiency of differentiation into neural stem-like cell. Results MSCs transfected with GFP-fusion wild ILK expressed ILK and kinase-dead mutant ILK stably. The activity of proliferation increased and more of them differentiated into neural stem-like cell, which express CD133 and Nestin validated by PCR and Western blotting, and more of wild than of mutant. Conclusion Integrin-linked kinase may play a positive role in MSC differentiation into neural stem-like cell, which may associate with the activity of kinase.

Objective Utilization of proteome method,by observing differences on protein expression of hypothalamus in the hyperthyroidism rats with hyperactivity of liver-yang and normal rats,to search the differential protein.Methods Models of animal were prepared by ip L-T4 and Fuzi Decoction.Both the quantitative and qualitative changes of the protein expression were compared between model group and treated group by protein technique.Results Proteins were mainly displayed at range of pI 3～8,Mr(14.4～75)kD.18 protein increased and 24 protein decreased in model group compared with treated group, included Thioredoxin,Ubiquitin carboxyl-terminal hydrolase isozyme L1,Platelet-activating factor acetylhydrolase IB gamma subunit,glutamate dehydrogenase,dihydropyrimidinase-related protein 2, NSFL1 cofactor p47,Tubulin beta 5.Conc(?)sion There were 18 spots high expressed and 24 spots low expressed in the hyperthyroidism with hyperactivity of liver-yang,that maybe related with the develepment of the hyperthyroidism with hyperactivity of liver-yang.

ObjectiveTo determine the effect of telmisartan on the levels of serum adiponectin and C-reactive protein(hs-CRP)in elderly hypertensive patients with unstable angina pectoris. MethodsOne hundred and twenty elderly hypertensive patients with unstable angina pectoris were randomized into two groups, telmisartan(n=60) and perindopril(n=60) groups.The levels of hs-CRP,adiponectin, lipid factors, fasting plasma glucose (FPG), insulin and insulin sensitivity index (ISI) were measured before and 6 months after telmisartan and perindopril treatments.ResultsAt the end of 6 months, the telmisartan group showed more reduction in plasma levels of hs-CRP and more increment in serum adiponectin concentrations and ISI significantly. The frequency of cardiovascular events was significantly lower in the patients of the telmisartan group than that of the perindopril group.ConclusionsCompared with perindopril, telmisartan significantly decreases plasma levels of hs-CRP and increases serum adiponectin concentrations in elderly hypertensive patients with unstable angina pectoris. It also significantly decreases the frequency of cardiovascular events in these patients.