To provide supports for Ginkgo biloba cell engineering for production of Terpene lactones (Ginkgolides and bilobalide), the cell suspension were established from calli induced from zygote embryos and stems of 30-day-old seedlings respectively. The relationship between cell growth, differentiation and the terpene lactone accumulation in these suspension cultures were investigated. HPLC determination indicated that, the ginkgolide B was found in the embryo derived cell suspension cultures at 0.044% of cell dry weight, and this result was the first time reported in this study. The accumulation of terpene lactone in the suspension cultures derived from both the embryo and seedling stems are effected by the level of the cell differentiation. The ginkgolide B was only found in small cell aggregates in the size smaller than 2mm, and the highest level of ginkgolide B was accumulated in cell aggregates in the size smaller than 1mm; however, the cell aggregates in the size bigger than 3mm could only produced bilobalide and ginkgolide A. In the same size aggregates of the suspension cultures the terpene lactone accumulation is strongly effected by the source of the explant. When the size of cell aggregates was in less than 1mm, the concentration of bilobalide, ginkgolide A and B in the cell suspension cultures derived from the embryos was 2, 1.4 and 0.56-fold, respectively, higher than that of cell cultures derived from seedling stems.
Bilobalides ; analysis ; Cell Differentiation ; physiology ; Cell Proliferation ; Culture Techniques ; methods ; Ginkgo biloba ; growth & development ; metabolism ; Ginkgolides ; analysis ; Lactones ; analysis

In this study, the HPLC-ELSD method was adopted to detect the equilibrium solubility of B and A in water and different pH buffer solution, as well as their apparent oil-water partition coefficients in the noctanol-water/buffer solution. Furthermore, the mass fraction weight coefficient method was adopted to express the integrated equilibrium solubility and oil-water distribution coefficient of ginkgolide components. The direct addition method and the mass fraction weight coefficient method were compared in calculating the property value of ginkgolide components, showing that the mass fraction weight coefficient method was more scientific and reasonable. The tentative study provided ideas to property characterization of traditional Chinese medicine components, as well as basis for studies on preparations of traditional Chinese medicine components.
Ginkgolides ; chemistry ; Hydrogen-Ion Concentration ; Medicine, Chinese Traditional ; Solubility

Traditional Chinese medicine (TCM) composition is a multi-component multiple drug release system and more components preparation system. How to evaluate the drug release behavior of diversification has been a block for the modernization of TCM. This article through to study of more representative components of ginkgolides drug release and similarity analysis of more representative components of ginkgolides drug release behavior and use Weight coefficient method to integrate the multicomponent drug release curve. So it can provide the idea and method for drug evaluation of TCM component preparation.
Drugs, Chinese Herbal ; chemistry ; Ginkgolides ; chemistry ; Kinetics ; Solubility

Microcrystalline cellulose and chitosan were applied to prepare ginkgolides component solid dispersions micro pill drug release unit and study the dissolution of GKS. Microcrystalline cellulose, chitosan as composite carrier, solvent method was used to prepare ginkgolides component solid dispersions. Differential scanning calorimetry was used to Characterization of ginkgolides component solid dispersions. Ginkgolides component solid dispersions as principle agent were prepared for micro-pellet. Comparison of different types, different doses of the adhesive, drug-polymer interactions, and disintegrating agent for the preparation of ginkgolides components of micro-pellet drug release unit, the optimum preparation ginkgolides components of micro-pellet drug release unit was screened by orthogonal design experiment. Preparation of ginkgolides components solid dispersions with microcrystalline cellulose and chitosan at ratio 1: 3. Drug cumulative dissolution was more than 80% in 60 min. Solid dispersion-micro-pellet drug release unit can significantly improve the dissolution of ginkgolides components, it has practical application value.
Cellulose ; chemistry ; Chitosan ; chemistry ; Drug Compounding ; methods ; Ginkgolides ; chemistry

The fragmentation pathways of the three ginkgolides (ginkgolides A, ginkgolides B, ginkgolides C) have been studied with high resolution and high mass accuracy using quadrupole time-of-flight mass spectrometry in negative ion mode in this paper. The results indicate that the three ginkgolides have similar fragmentation pathways, including four kinds of common cleavage pathways and one common characteristic ion. In high quality regions, the typical fragmentation pathways of the three ginkgolides are lactone ring opening with continuous loss of CO, CO₂,and loss of H₂O. In low quality regions, the common characteristic fragment ion of the three ginkgolides at 72.993 6 is formed by C rings cleavage. Also, the common fragment ions of ginkgolides A and ginkgolides B at 141.018 8, 125.023 8, 113.024 0, 97.029 1 are formed by A rings cleavage. The study of fragmentation pathways could be adopted for the structural identification of the ginkgolides and their metabolites.
Ginkgolides ; chemistry ; Mass Spectrometry ; Spectrometry, Mass, Electrospray Ionization

Ginkgolides,the unique terpenoids in Ginkgo biloba,have a significant effect on the prevention and treatment of cardiovascular and cerebrovascular diseases. Metabolic regulation and synthetic biology strategies are efficient methods to obtain high-quality ginkgolides. The present study reviewed the cloning and functions of genes related to the biosynthetic pathway of ginkgolides,as well as relevant studies of omics,genetic transformation,and metabolic regulation in recent years,and predicted the research trends and prospects,aiming to provide a reference for discovering the key genes related to the biosynthetic pathway and the biosynthesis of ginkgolides.
Ginkgo biloba/genetics* ; Ginkgolides ; Humans ; Lactones ; Plant Extracts ; Terpenes

To prepare a new dosage form that can improve the drug loading of the film--ginkgolide B nanosuspension lyophilized powder orodispersible film(GB-NS-LP-ODF) and to evaluate its quality. Firstly, ginkgolide B nanosuspension(GB-NS) was prepared by media milling method, and then ginkgolide B nanosuspension lyophilized powder(GB-NS-LP) was prepared with freeze-drying method. The mannitol was used as lyoprotectant and its dosage was also investigated. GB-NS-LP-ODF was prepared by solvent casting method and its formulation was screened by single factor test method and optimized by orthogonal test. The appearance, mechanical properties, content uniformity and in vitro dissolution of the optimized GB-NS-LP-ODF were investigated. The particle size of prepared GB-NS was about 201 nm, and the optimal dosage of mannitol was 8%. According to the optimal formula, the GB-NS-LP-ODF was prepared with GB-NS-LP 35.6%, PVA 0588 49.4%, PEG 400 10.7% and CMS-Na 4.3%, and completely disintegrated in about 30 s, and the particle size of reconstituted GB nanoparticles from ODF was about 210 nm. The film with smooth appearance and good mechanical properties was stable within 30 days and the content uniformity(A+2.2 S<15) conformed to the regulations. Scanning electron microscope(SEM) showed that GB-NS-LP-ODFs were evenly distributed and the particle size was about 200 nm. X-rays diffraction(XRD) showed that its crystallinity was significantly lower than that of GB raw drug and GB-ODF. The results of in vitro release test showed that the drug film was completely dissoluted within 10 minutes. These results indicated that nanosuspension lyophilized powder was prepared by freeze drying of nanosuspensions, and then loaded into the orodispersible film to effectively increase the drug loading of the ODF and have broad application prospects.
Ginkgolides ; Lactones ; Nanoparticles ; Particle Size ; Powders ; Solubility ; Suspensions

OBJECTIVETo optimize the preparation process of solid dispersions of ginkgolides to improve the drug dissolution.

METHODThe influence of formulation and preparation technology on drug release from solid dispersions was investigated by single factor test. The X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) were used to characterize the solid dispersions of ginkgolides.

RESULTThe solubilization efficiency of solid dispersions using PVP k30 as carrier was better than that taking poloxamer 188 or HPMC as matrix. The results of XRD and DSC showed that ginkgolides existed in solid dispersion at amorphous form or solvates form. The dissolution rate of ginkgolide B in solid dispersion was increased dramatically compared with raw material.

CONCLUSIONSolid dispersions could significantly improve solubility and dissolution rate of ginkgolides.

Calorimetry, Differential Scanning ; Ginkgolides ; chemistry ; Pharmaceutical Preparations ; chemistry ; Solubility ; X-Ray Diffraction

OBJECTIVETo optimize the formulation of long-circulating solid lipid nanoparticles (LSLN) carrying ginkgolides A and B (GAB) extracted from traditional Chinese medicinal herbs.

METHODSGAB-LSLN was prepared by high pressure homogenization. The effects of such factors as the contents of glycerol monostearate, soybean lecithin and Myrj 59 on the mean diameter, entrapment efficiency and drug loading were investigated using central composite design and response surface method. The data were analyzed using multi-linear equation and second-order polynomial equation for selecting the optimal conditions for LSLN preparation.

RESULTSThe method of second-order polynomial equation was superior to multi-linear equation method in view of the multiple correlation coefficients. Under the optimal conditions, the mean diameter, entrapment efficiency, and drug loading of the GAB-LSLN were 169.5 nm, 92.3% and 5.1%, respectively.

CONCLUSIONThe optimized process for GAB-LSLN preparation is stable, feasible and allows high inclusion rate in the large-scale production of GAB-LSLN.

Delayed-Action Preparations ; chemical synthesis ; chemistry ; Drug Compounding ; methods ; Ginkgolides ; chemistry ; Lactones ; chemistry ; Liposomes ; Nanoparticles ; chemistry

Having searched a large number of literatures, the author found different concepts of traditional Chinese medicine components among pharmacists. Then, what are traditional Chinese medicine components? The author thinks that traditional Chinese medicine components shall be optimized traditional Chinese medicine components with relatively clear efficient substances, action mechanisms, specific purity and definite internal structure. This experiment preliminarily determined optimized component structures of ginkgolides by comparing the four reported constituents in in vivo and in vitro pharmacodynamic and pharmacological experiments. The experimental design could provide ideas and basis for optimizing traditional Chinese medicine components and determining their matching structures.
Animals ; Ginkgolides ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Mice ; Research Design