ABSTRACT
This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals. Specifically, the nanocrystals were prepared with daidzein as a model drug, PEG_(20000), Carbomer_(940), and NaOH as a plasticizer, a gelling agent, and a crosslinking agent, respectively. A two-step method was employed to prepare the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocystals. First, the insoluble drug daidzein was embedded in β-cyclodextrin to form inclusion complexes, which were then encapsulated in the PEG_(20000)/Carbomer_(940) nanocrystals. The optimal mass fraction of NaOH was determined as 0.8% by the drug release rate, redispersability, SEM morphology, encapsulation rate, and drug loading. The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR), thermogravimetric analysis(TGA), and X-ray diffraction(XRD) analysis to verify the feasibility of the preparation. The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading, respectively. The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM. The redispersability experiment showed high dispersion efficiency of the nanocrystals. The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein, and followed the first-order drug release kinetic model. XRD, FTIR, and TGA were employed to determine the polycrystalline properties, drug loading, and thermal stability of the nanocrystals before and after drug loading. The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect. The nanocrystals had more significant inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein. The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.
Subject(s)
Sodium Hydroxide , Acrylic Resins , Escherichia coli , NanoparticlesABSTRACT
ObjectiveTo investigate the long-term safety of triptolide ferulic acid ethosome gel in percutaneous administration. MethodWe mixed triptolide with ferulic acid to make liposomes gel in different doses and then administrated the gel to SD rats of both sexes with intact skin and damaged skin for 12 weeks. The daily dosages calculated based on triptolide for the low-， middle-， and high-dose groups were 63.75， 127.50， 255.00 μg·kg-1， respectively. The body weight of each rat was measured weekly. The rats were sacrificed in the last week for the determination of serum biochemical parameters and organ indexes as well as the observation of histopathology. The toxicity was assessed based on the body weight and all the parameters and indexes. ResultAfter long-term administration， the body weight and serum biochemical parameters did not show significant difference between the gel-treated groups and the blank group with intact skin， which indicated that the percutaneous administration of triptolide and ferulic acid ethosomes gel was relatively safe. However， the rats in the high-dose group showed sparse hair and were easy to die in the case of unhairing with chloral hydrate at the late stage of the study. Comprared with the female rats with intact skin in the blank control group， the female rats with damaged skin in the middle-dose group showed decreased heart index （P<0.05）， which indicated certain cardiotoxicity. Moreover， damage appeared in skin and lung， which may be influeneced by dosage， sex， and skin state. ConclusionFerulic acid in combination with triptolide is relatively safe for percutaneous administration， whereas there are some risks of skin and lung damage in the case of long-term administration. Individualized administration scheme should be developed according to liver and kidney function and skin conditons to ensure the safety of clinical medication.
ABSTRACT
A total of 15 batches of the substance reference of Guizhi Jia Gegen Decoction(GZGGD) were prepared and the characteristic fingerprints of them were established. Furthermore, the similarity of the fingerprints and peak attributes were explored. The extraction rate, and the content and the transfer rate ranges of the index components, puerarin, paeoniflorin, liquiritin, and ammonium glycyrrhizate were determined for the analysis of the quality value transfer. The result demonstrated that the fingerprints of the 15 batches of the samples showed high similarity(>0.99). A total of 15 characteristic peaks were identified from the fingerprints, with 10 for Puerariae Lobatae Radix, 1 for Cinnamomi Ramulus, 2 for Paeoniae Radix Alba, and 2 for Glycyrrhizae Radix et Rhizoma. The content of puerarin was 11.05-18.35 mg·g~(-1) and the average transfer rate was 21.27%-39.49%. The corresponding figures were 7.95-10.90 mg·g~(-1) and 23.28%-43.23% for paeoniflorin, 3.25-4.95 mg·g~(-1) and 32.31%-61.27% for ammonium glycyrrhizate, and 3.65-5.80 mg·g~(-1) and 14.57%-27.05% for liquiritin. The extraction rate of the 15 batches of samples was in the range of 16.85%-21.78%. In this paper, the quality value transfer of the substance reference of GZGGD was analyzed based on characteristic fingerprint, content of index components, and the extraction rate. This study is expected to lay a basis for the quality control and further development of GZGGD.
Subject(s)
Ammonium Compounds , Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , PaeoniaABSTRACT
The present study explored the drying effect of new spiral vibration drying technology on Chinese medicinal pills with Liuwei Dihuang Pills, Zhuanggu Guanjie Pills, and Muxiang Shunqi Pills as model drugs. With the drying uniformity, drying time, energy consumption, pill split, dissolution time, and change of index components as evaluation indicators, the drying effect of spiral vibration drying technology on model drugs was evaluated and compared with traditional drying methods, such as hot air drying and vacuum drying in the oven. The dynamic changes of moisture in Liuwei Dihuang Pills with different drying time were investigated. Compared with the traditional drying methods in the oven(hot air drying and vacuum drying) at 80 ℃, the spiral vibration drying only took 80 min, shortened by 80%, with 10%-13% energy consumed. The results showed that the moisture of Liuwei Dihuang Pills was negatively related to the drying time. By virtue of multi-layer countercurrent drying and super resonant fluidization techniques, the new spiral vibration drying technology can significantly improve the drying quality of Chinese medicinal pills, improve the drying efficiency, and enhance the manufacturing capacity of Chinese medicinal pills. This study is expected to provide references for the innovation and development of new drying technology of Chinese medicinal pills.
Subject(s)
China , Desiccation , Physical Therapy Modalities , Technology , VibrationABSTRACT
With advanced brewing technology and contemporary table culture， alcohol drinking， which can be traced back to Dukang wine in the Xia dynasty， is very common in China. However， excessive alcohol intake can easily cause alcohol liver damage， ranging from abdominal pain and venous thrombosis to severe hypoglycemia and fat embolism， coma shock and even life-threatening cases. Puerariae Lobatae Radix has a cool property and sweet taste， with functions of antipyretic， promoting the secretion of saliva or body fluid， rash and hangover alleviation， and so on. It was first recorded in Shen Nong's Materia Medica and has been listed as a special anti-alcoholic medicine in traditional Chinese medicine since ancient times. For example， the ancient medical book Compendium of Materia Medica and other records claim that Puerariae Lobatae Radix has the effect of relieving alcohol and protecting the liver. At the same time， Puerariae Lobatae Radix has a long history in both medicine and food. It was listed in the List of Articles That Both Serve as Food and Medicine published by the National Health Commission. Therefore， there are many products containing pueraria for hangover and liver protection. Prior to this， many scholars have carried out relevant researches on the anti-alcoholism efficacy of Puerariae Lobatae Radix， but there is a lack of systematic summaries. The author has consulted relevant domestic and foreign literatures in recent years. The related products were summarized and it was found that the anti-alcoholic effect of pueraria root mainly came from puerarin， pueraria flavonoids and pueraria polysaccharide， puerarin polypeptide， pueraria daidzein and its derivatives， including the main mechanisms such as inhibiting alcohol absorption， accelerating metabolism， anti-oxidation， protection of liver and cardiomyocytes， and neuroprotection. Related products are abundant and well evaluated， but research on related genes needs to be deepened. This article reviews the main anti-alcoholic components， mechanism of action and related products of pueraria， and puts forward suggestions for future research directions， hoping to provide reference for further related research.
ABSTRACT
Volatile oil is widely distributed in Chinese medicinal materials with complex chemical components. The main components are terpenes， aromatics， aliphatics， and nitrogen and sulfur containing. It has a variety of pharmacological activities. Such as antibacterial， anti-inflammatory， analgesic， anti-tumor， anti-oxidant， anti-aging and so on. It is widely used in medical and health care， agricultural efficiency enhancement， and daily products. In recent years， there have been a large number of studies on the pain relief of traditional Chinese medicine （TCM） essential oils， but there is no systematic generalization. The author found that the mechanism of TCM essential oils to exert analgesic effects mainly includes regulation of the central nervous system， anti-inflammatory and analgesic， antispasmodic and analgesic effects by consulting Chinese and foreign literatures in recent years， but the exact mechanism needs to be further verified. This article reviews the research progress of TCM essential oil pain relief from the aspects of pain classification， generation， analgesic mechanism and combination of other technologies， in order to provide reference for related research in the future.
ABSTRACT
In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.
Subject(s)
Administration, Cutaneous , Drugs, Chinese Herbal , Liposomes , Oils, Volatile , Particle Size , SolubilityABSTRACT
To further investigate the metabolism of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel in vivo,an LCMS/MS method was established for the determination of triptolide and paeoniflorin in T. wilfordii and P. lactiflora micro-emulsion gel.The extracorporeal recovery rate of blood probe was measured by concentration difference methods( incremental method and decremental method). Meanwhile,the skin and blood micro-dialysis methods of tripterine and paeoniflorin were established,and the pharmacokinetics of T. wilfordii microemulsion gel in skin and blood was studied by micro-dialysis combined with LC-MS/MS quantitative analysis. The results showed that the established method for the determination of triptolide and paeoniflorin in T. wilfordii microemulsion gel was well linear within the required range,and the specificity,recovery rate and degree of precision of the chromatography all conformed to the research requirements of micro-dialysis samples. The stability of freeze-thawing and the residual effect all conformed to the criteria of biological sample methodology. The probe recovery rates measured by incremental method and decremental method were almost consistent with the extracorporeal recovery rate test. The recovery rates of paeoniflorin in skin and blood micro-dialysis were( 30. 60±1. 09) % and( 28. 01± 1. 75) %,respectively. And the recovery rates of skin and blood micro-dialysis were( 26. 79 ± 2. 78) % and( 25. 39±1. 86) %,respectively. The intraday recovery rate of probes was stable within 11 h. The results of pharmacokinetic study showed that the Cmaxvalues of triptolide in skin and blood were( 148. 03±41. 51) and( 76. 77±15. 27) μg·L-1,respectively. And the Tmaxvalues were( 2. 33±0. 29) and( 3. 00± 0) h,respectively. The AUC0-11 hvalues were( 2 814. 05± 1 070. 37) and( 1 580. 63±208. 27) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 20± 0. 33) and( 4. 54± 0. 34) h,respectively. The T1/2 values were( 4. 61±4. 11) and( 1. 07± 0. 13) h,respectively. The Cmaxvalues of paeoniflorin in skin and blood were( 991. 88 ± 152. 22) and( 407. 02±120. 06) μg·L-1,respectively. The Tmaxvalues were( 2. 00±0) h and( 2. 83±0. 29) h,respectively. The AUC0-11 hvalues were( 18 430. 27±3 289. 35) and( 6 338. 59 ± 1 659. 32) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 29 ± 0. 16) and( 4. 00±0. 05) h,respectively. The T1/2 values were( 2. 16±0. 43) and( 1. 78±0. 48) h,respectively. The results suggested that micro-emulsion gel played a role in forming skin reservoir through percutaneous penetration. It not only could improve drug transdermal efficiency,but also control the sustained release of drug and form a long-term effect.
Subject(s)
Humans , Blood , Metabolism , Chromatography, Liquid , Drugs, Chinese Herbal , Pharmacokinetics , Emulsions , Gels , Paeonia , Chemistry , Skin , Metabolism , Tandem Mass Spectrometry , Tripterygium , ChemistryABSTRACT
To detect the concentration of triptolide in skin and joint after percutaneous administration,an HPLC-MS/MS method and skin and joint micro-dialysis( MD) method of triptolide were established in this study. The separation was achieved on triple quadrupole( AB QTRAP4500) and phenomenex-C18( 4. 6 mm×150 mm,5 μm,luna) column with acetonitrile-water with 0. 1% formic acid( 65 ∶35) as the mobile phase at a flow rate of 0. 7 m L·min-1. An electrospray ionization( ESI) source was applied and operated in the positive multiple reaction monitoring( MRM) mode. The fragment ion for triptolide was m/z 361. 1→145. 0. The effects of different perfusion [Ringer's,PBS( p H 7. 4),30% ethanol saline]drug concentrations and flow rates on the recovery rate,as well as the relationship between the recovery rate and the loss rate were determined by incremental( dialysis) and reduction( retrodialysis) methods.The reduction method was applied in the in vivo study to investigate and determine the stability of the probe recovery rate in 10 h. The results of HPLC-MS/MS detection method conformed to the requirements of biological samples. The perfusion fluid was 30% ethanol saline. The recovery rate of skin and joint probes in vitro of triptolide increased within the flow rate of 0. 5-2. 5 μL·min-1. In order to increase the timeliness of data and the accuracy,the flow rate was determined to be 1 μL·min-1,and the sample interval was determined to be 0. 5 h. The recovery rate of triptolide in skin and joint probes in vitro and the loss rate were stable and equal despite of change of triptolide concentration within 10-200 μg·L-1. This indicated that the effect of drug concentration on the MD probe recovery rate was small,and the recovery rate could be replaced by the loss rate. The loss rate in vivo using MD method was measured at 10 h,indicating that the transfer rate of triptolide was stable within 10 h. The established method of triptolide in MD and HPLC-MS/MS can be applied to investigate the kinetic in skin and joint after percutaneous administration of triptolide.
Subject(s)
Humans , Chromatography, High Pressure Liquid , Diterpenes , Pharmacokinetics , Epoxy Compounds , Pharmacokinetics , Joints , Metabolism , Phenanthrenes , Pharmacokinetics , Reproducibility of Results , Skin , Metabolism , Tandem Mass SpectrometryABSTRACT
The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption, and investigate the mechanism of permeation on the microstructure and molecular structure of stratum corneum. Through the determination of stratum corneum/medium partition coefficient of ferulicacid in Chuanxiong influenced by Frankincense and Myrrh essential oil, the effects of volatile oil of frankincense and Myrrh on the the microscopic and molecular structure of stratum corneum were explored by observation of skin stratum corneum structure under scanning electron microscopy, and investigation of frankincense and myrrh essential oil effects on the molecular structure of keratin and lipids in stratum corneum under Fourier transform infrared spectroscopy. The results showed that the oil could enhance the distribution of ferulic acid in the stratum corneum and medium, and to a certain extent damaged the imbricate structure of stratum corneum which was originally regularly, neatly, and closely arranged; some epidermal scales turned upward, with local peeling phenomenon. In addition, frankincense and myrrh essential oil caused the relative displacement of CH2 stretching vibration peak of stratum corneum lipids and amide stretching vibration peak of stratum corneum keratin, indicating that frankincense and myrrh essential oil may change the conformation of lipid and keratin in the stratum corneum, increase the bilayer liquidity of the stratum corneum lipid, and change the orderly and compact structure to increase the skin permeability and reduce the effect of barrier function. It can be concluded that Frankincense and Myrrh essential oil can promote the permeation effect by increasing the distribution of drugs in the stratum corneum and changing the structure of the stratum corneum.