OBJECTIVETo compare the influence on the dissolution of tanshinone IIA (TS IIA) solid dispersions in complex carriers and single, which used in preparation of TS IIA solid dispersions, and further enhance the dissolution of TS IIA.

METHODThe TS IIA solid dispersions were prepared by solvent technique with polyvinylpyrrolidone K30 (PVPK30), poloxamer188 (F68) and combination of PVPK30 and F68 as carriers, respectively. The physical characteristics of TS IIA solid dispersions was studied using differential scanning calorimetry (DSC). Dissolution rates were studied using small cup method (CHP XC III). The solubility of TS IIA with the solid dispersions and pure drug form were determined by HPLC method.

RESULTThe DSC analysis suggested that TS IIA was dispersed as an amorphous form in the combination of PVPK30 and F68. Dissolution profile of the prepared solid dispersions could be described by Weibull equation (R>0.99). For tested three carries, Td value (calculated time to 63.2% of total drug release according to Weibull equation) were (90.40 +/- 2.82) min, (204.5 +/- 8.20) min and (25.83 +/- 0.13) min, respectively. The PVPK30/F68-TS IIA solid dispersion resulted in a significant increase of TS IIA solubility compared with prepared PVPK30-TS IIA and F68-TS IIA solid dispersions (P<0.01).

CONCLUSIONAs compared to single use of PVPK30 or F68, the combination of PVPK30 and F68 improve the dissolution rate and solubility of TS IIA significantly in the prepared solid dispersions (P<0.01). The application of complex carriers in solid dispersion technology should be paid more attention to improvement of poorly soluble drugs dissolution in the future.

Diterpenes, Abietane ; Phenanthrenes ; chemistry ; Solubility ; Temperature

OBJECTIVETo analyze the content of tanshinone IIA in Radix Salviae Miltiorrhizae from different habitats are regularly altered and find out the deviation between the studies.

METHODThe data of the content of tanshinone IIA in samples of Radix Salviae Miltiorrhizae from different areas and related information since 1997 was collected and statistically analyzed.

RESULT AND CONCLUSIONThe content of tanshinone IIA in wild Salvia was generally higher than that in the cultivated Salvia, and the content in nearly half cultivated Salvia was less than 0.2%. There existed a big difference between the used statistical model, and the data related the content in samples from Sichuan was the most divisive. The coefficient of variation of wild Salvia was below the cultivated Salvia, and the cultivated Salvia from different areas showed different coefficients of variation. The content of tanshinone IIA was lower when samples were extracted using the heating reflux method.

Diterpenes, Abietane ; Phenanthrenes ; analysis ; Salvia miltiorrhiza ; chemistry

Introduction: Opioid dependence is recorded as the most common drug of abuse in Malaysia. Currently, the preferred substitution therapy for most Government treatment centres is methadone used as substitution therapy for opioid dependence. There are, however patients who may benefit from being on the combined buprenorphine-naloxone formulation as substitution therapy instead. We discuss six cases of opioid dependence of varied backgrounds that were treated with buprenorphinenaloxone therapy and their outcomes. Discussion: All of the reported patients improved after the induction of buprenorphine- naloxone. Two of the cases highlighted the transfer of patients on methadone to buprenorphine-naloxone due to the adverse effect and interactions of methadone with other medications. During the transfer there were no major adverse reactions noted, and patients were safely able to continue with the maintenance therapy of buprenorphine- naloxone. Conclusion: Buprenorphine-naloxone is a safe and effective drug substitution therapy for opioid dependence. It has fewer interactions with other medications, and has similar efficacy to methadone. Being a partial agonist, it has a less sedating effect making patients more functional.
Buprenorphine, Naloxone Drug Combination

The fibrous roots are the residues of production of cut crude drug of Danshen (Salvia miltiorrhiza). Enzymatic pretreatment and ultrasonic extraction are beneficial to extract effective constituents from fibrous roots more effectively. The present research was to optimize the enzymatic parameters by the central composite design and response surface method. Under the best conditions, the yields of total tanshinones and total salvianolic acids in the extracts of enzymatic pretreatment increased by 113.92% and 30.64%, comparing with the non-enzymatic extraction, respectively. TLC analysis also showed that the types of effective constituents in the two samples were not affected by enzymatic hydrolysis. Meanwhile, the complex correlation coefficients of the mathematical models were high, which provided a good prediction.
Diterpenes, Abietane ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo establish a method to determine the dissolution of Tanshinone IIA in xianling gubao capsules, and compare the dissolution of Xianling Gubao capsules prepared by different processes.

METHODThe small cup method was used at a rotary speed of 100 r x min(-1), the dissolubility was inspected in the following 6 mediums: (1) water; (2) 0.1 mol x L(-1) hydrochloric acid solution; (3) pH 6.8 phosphate buffer; (4) pH 6.8 phosphate buffer solution + 0.5% cholic acid; (5) pH 6.8 phosphate buffer solution + 1.0% cholic acid; (6) pH 7.6 phosphate buffer solution + 4. 0% cholic acid. A HPLC method was used to determine the dissolution samples of tanshione IIA in different dissolution mediums. The accumulative dissolution percentages were calculated, and the resemblance of release curves were compared by similarity factors (f2).

RESULTThe accumulative dissolution percentage was the highest while pH 7.6 phosphate buffer solution + 4.0% cholic acid was used as medium. The similarity factor values (f2) of tanshinone IIA dissolution curves of different preparation processes of Xianling Gubao capsules were all less than 50.

CONCLUSIONThere is significant difference in tanshinone IIA dissolution between Xianling Gubao capsules of different preparation processes. The accumulative dissolution percentages of the tanshinone IIA in new Xianling Gubao capsules is higher than that in the capsules prepared by other preparation processes.

Capsules ; Chromatography, High Pressure Liquid ; methods ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; Solubility

OBJECTIVETo establish a new method using AOTF-Near infrared spectroscopy (NIRS) for quick determination of tanshinone II(A) and salvianolic acid B in Fufang Danshen tablets.

METHODHPLC was used as a reference method to determine the contents of tanshinone II(A) and salvianolic acid B in Fu Fang Dan Shen tablets. Multivariate calibration models based on PLS1 algorithm were developed to correlate the spectra and the corresponding values determined by the reference methods.

RESULTRMSECV (root-mean-square error of cross-validation) of the models for tanshinone II(A) and salvianolic acid B were 0.0103 and 0.1868 respectively. The correlation coefficients of the calibration models were 0.9873 and 0.9832 respectively. External validation with external validation samples proved that the relative coefficient of the predicted value and the truth value were R2 = 0.9743 and R2 = 0.9886 respectively, with measured recycle rates of 103.0% and 99.0%.

CONCLUSIONNIRS can be used in the determination of tanshinone II(A) and salvianolic acid B, which sets up the foundation of product-line control of Fuang Danshen tablets.

Benzofurans ; analysis ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; analysis ; Reproducibility of Results ; Spectroscopy, Near-Infrared ; methods ; Tablets ; chemistry

The study is aimed to investigate the effect of plant growth regulators on yield and quality of the Salvia miltiorrhiza. The plant growth regulators was spraying on Salvia plants in July or August in field experiment, then the yield, ingredient content and the antioxidant activity were determined. The results showed that plant growth regulator 'Zhuanggenling' could increase the yield of Salvia with root-planting by 38.45%. Plant growth regulator 'Duoxiaozuo' could increase the yield of Salvia with seedling planting by 14.19%. Both plant growth regulator significantly reduced the antioxidant activity of Salvia in vitro, but they had no significant effect on active ingredient contents.
Diterpenes, Abietane ; analysis ; Phenanthrenes ; analysis ; Plant Extracts ; analysis ; Plant Growth Regulators ; pharmacology ; Salvia miltiorrhiza ; chemistry ; drug effects ; growth & development

OBJECTIVETo develop an identitication and quantitation method for Radix Salviae Miltiorrhizae.

METHODThe powder X-ray Diffraction Fourier Fingerprint Pattern technique was used for this purpose. The high performance liquid chromatography method was used to evaluate the quantity of Tanshinone II A in 9 samples and 1 drug reference substance. The relationship of diffraction peak intensity and content of Tanshinone II A was investigated.

RESULT AND CONCLUSIONThe powder X-ray diffraction Fourier Fingerprint Pattern analysis technique can be used to identify Radix Salviae Miltiorrhizae and to evaluate the quantity of Tanshinone II A in the drug at the same time.

Chromatography, High Pressure Liquid ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; Salvia miltiorrhiza ; chemistry ; X-Ray Diffraction ; methods

OBJECTIVETo explore the optimal supercritical-CO2 fluid extraction technique of extracting tanshinones in Radix salviae.

METHODThe contents of tanshinones were determined by HPLC. Choosing the overall contents of 3 tanshinones as inspecting marker and uniform-design as method, the experimentation was carried out to study the main factors that influence the result of extraction.

RESULTAmong all the 5 inspected factors, the amount of entrainer was most notable. The optimal technique of extraction was: extraction pressure at 30 MPa; extraction temperature at 40 degrees C; separation pressure of separating kettle I at 6 MPa; separation temperature of separating kettle I at 50 degrees C; the amount of entrainer at 10%.

CONCLUSIONAdopting supercritical-CO2 fluid extraction method to extract the tanshinones in Radix salviae was feasible. The contents of tanshinones in the extract were high and the manipulation was simple, convenient and time saving.

Carbon Dioxide ; Chromatography, Supercritical Fluid ; methods ; Diterpenes, Abietane ; Phenanthrenes ; isolation & purification ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry

Taking Tanshinon IIA as the target and using reversed phase high performance liquid chromatography,we have developed a rapid and sensitive assay for lipophilic components of Danshen (LCD) in perfusate. The model of intestinal absorption was used to determine the concentration of Tanshinon IIA in rats as an in situ model. The change of concentration of Tanshinon IIA was separately calculated according to Michaelis-Menten and the Fick's equation to investigate the absorptive limit step of the LCD. It was concluded that the limit step to absorption of LCD was at the dissolution, by assessing the fitting index or correlative index. On the basis of the conclusion, the experiment was designed to prepare the inclusive complex of the LCD with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and to study its absorptive mechanism. With the increase of dosage of complex, its absorption did not show saturated phenomenon in gastro-intestinal tract in rats and the constant Ka did not show significant difference, suggesting that the transport of mechanism in vivo is similar to passive transport.
2-Hydroxypropyl-beta-cyclodextrin ; Biological Transport ; Chromatography, High Pressure Liquid ; Diterpenes, Abietane ; Intestinal Absorption ; Phenanthrenes ; isolation & purification ; pharmacokinetics ; Salvia miltiorrhiza ; chemistry ; beta-Cyclodextrins ; chemistry ; pharmacokinetics