The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
Polysorbates/chemistry* ; Flavonoids ; Pueraria ; Surface-Active Agents/chemistry* ; Ethanol ; Emulsions ; Particle Size ; Solubility

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.
Polyethylene Glycols/chemistry* ; Castor Oil ; Methanol ; Surface-Active Agents/chemistry* ; Solvents ; Water/chemistry* ; Emulsions/chemistry*

A new quercetin nanocrystals self-stabilized Pickering emulsion(QT-NSSPE) was prepared by high-pressure homogenization combined with probe ultrasonic method. The influences of oil fraction, quercetin(QT) concentration, and pH of water phase on the formation of QT-NSSPE were investigated. On this basis, the QT-NSSPE prepared under optimal conditions was evaluated in terms of microstructure, stability, and in vitro release and the droplet size and drug loading were 15.82 μm and 4.87 mg·mL~(-1), respectively. The shell structure formed by quercetin nanocrystals(QT-NC) on the emulsion droplet surface was observed under a scanning electron microscope(SEM). X-ray diffraction(XRD) showed that the crystallinity of adsorbed QT-NC decreased significantly as compared with the raw QT. There were not significant changes of QT-NSSPE properties after 30 days of storage at room temperature. The in vitro release experiment confirmed that QT-NSSPE has a higher accumulative release rate than the raw QT. All these results indicated that QT-NSSPE has a great stability and a satisfactory in vitro release behavior, which is a promising new oral delivery system for QT.
Emulsions/chemistry* ; Nanoparticles ; Particle Size ; Quercetin ; Water/chemistry*

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.
Blood ; metabolism ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Emulsions ; Gels ; Humans ; Paeonia ; chemistry ; Skin ; metabolism ; Tandem Mass Spectrometry ; Tripterygium ; chemistry

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations.
Acorus ; chemistry ; Emulsions ; Oils, Volatile ; analysis ; standards ; Particle Size ; Plant Oils ; analysis ; standards ; Rhizome ; chemistry ; Solubility

Dogwood fruits are a valuable source of active ingredients, such as phenolic compounds, vitamin C, iridoids, flavonoids and anthocyanins. Plant extracts and substances derived from latin Cornus mas L. exhibit not only strong antibacterial but also antioxidant and tonicity properties, effectively preventing the development of inflammation in living organisms. In the present study, we attempted to obtain the innovative, multi-functional plant extract from the fruit of dogwood (Cornus mas L.). During the extraction process a mixture of water, glycerol, and vegetable oil were used as an extractant. The usage of such mixtures of solvents enabled us to extract a variety of active substances, soluble in both water and oils. The obtained extracts were analyzed for their physicochemical and biochemical properties, in order to apply the extract in a body nutrient lotion. The results clearly showed that such extract could be an innovative and multi-functional raw material used in cosmetics industry.
Adolescent ; Adult ; Antioxidants ; analysis ; Child ; Cornus ; chemistry ; Cosmetics ; chemical synthesis ; chemistry ; Emulsions ; chemical synthesis ; chemistry ; Female ; Flavonoids ; analysis ; Fruit ; chemistry ; Humans ; Irritants ; analysis ; Male ; Middle Aged ; Phenols ; analysis ; Plant Extracts ; chemistry ; Young Adult

The purpose of this study was to design and prepare a biocompatible microemulsion of Andrographis paniculata (BMAP) containing both fat-soluble and water-soluble constituents. We determined the contents of active constituents of BMAP and evaluated its bioavailability. The biocompatible microemulsion (BM), containing lecithin and bile salts, was optimized in the present study, showing a good physical stability. The mean droplet size was 19.12 nm, and the average polydispersity index (PDI) was 0.153. The contents of andrographolide and dehydroandrographolide in BMAP, as determined by high performance liquid chromatography (HPLC), were higher than that in ethanol extraction. The pharmacokinetic results of BMAP showed that the AUC0-7 and AUC0→∞ values of BMAP were 2.267 and 27.156 μg·mL(-1)·h(-1), respectively, and were about 1.41-fold and 6.30-fold greater than that of ethanol extraction, respectively. These results demonstrated that the bioavailability of and rographolide extracted by BMAP was significantly higher than that extracted by ethanol. In conclusion, the BMAP preparation displayed ann improved dose form for future clinical applications.
Andrographis ; chemistry ; Chemical Fractionation ; instrumentation ; methods ; Chromatography, High Pressure Liquid ; Diterpenes ; analysis ; isolation & purification ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; Emulsions ; chemistry

To explore the effect of long-time propofol infusion on myocardial enzymes, mitochondrial cytochrome C and ATP in rabbits. 
 Methods: A total of 18 New Zealand rabbits were randomly divided into 3 groups: a control group, a propofol group and an intralipid group. The rabbits were continuously infused with 0.9% normal saline in the control group, 1% propofol in the propofol group, and 10% intralipid in the intralipid group, respectivey. The arterial blood was collected at 0, 8, 16 h and the end of experiment to examine creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the end, the myocardial mitochondria from myocardial tissues was separated by differential centrifugation, and mitochondrial cytochrome C content and adenosine triphosphate (ATP) levels were examined by high performance liquid chromatography.
 Results: Compared with the control group, the release of cytochrome C from mitochondria were increased in the propofol group and the intralipid group (both P<0.05), but there was no significant difference between them (P>0.05). There was also no significant difference in the ATP content of the mitochondria among the 3 groups (P>0.05). The levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group compared with that before the infusion (all P<0.05); compared with the control group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group (all P<0.05); compared with the intralipid group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group (all P>0.05); compared with the control group, the levels of CK-MB were obviously increased in the infusion of propofol for 24 h in the propofol group (P<0.05).
 Conclusion: The levels of serum CK increase after the infusion of propofol and intralipid for a long time, and the levels of CK-MB also elevate in the infusion of propofol. Propofol and intralipid can increase the release of myocardial mitochondrial cytochrome C, but they don't affect the ATP production in myocardial mitochondrial.
Adenosine Triphosphate ; metabolism ; Animals ; Creatine Kinase ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Cytochromes c ; metabolism ; Emulsions ; administration & dosage ; pharmacology ; Infusions, Intravenous ; Mitochondria ; drug effects ; Myocardium ; chemistry ; enzymology ; Phospholipids ; administration & dosage ; pharmacology ; Polyphosphates ; Propofol ; administration & dosage ; pharmacology ; Rabbits ; Soybean Oil ; administration & dosage ; pharmacology

Due to the irregular of diet and overfeeding greasy and surfeit flavor closely associated with hyperuricemia disease, the lipid emulsion containing high cholesterol was used to model. To obtain a more stable and sustained animal model for the efficacy evaluation of traditional Chinese herbs, we observed the influence on the serum uric acid of rat induced by the lipid emulsion compared with high purine diet. 36 SD male rats were randomized to the normal control group, high purine diet group and lipid emulsion group respectively. The general behavior, body weight and daily food intake of rats were observed. The orbital blood was taken to separate into the serum and 24 hours urine was collected. The serum indexes such as UA, BUN, Cr, ALT, AST, TC, TG, LDL-c were determined every 2 weeks, and XOD, ADA enzyme activity were determined at the 4th week. The urine indexes such as UA, Cr and Cua/Ccr were determined at the 4th week. After stopping modeling, the serum UA were determined two weeks and four weeks later respectively. At the 2nd week, the body weight and daily food intake of rats in the lipid emulsion group reduced significantly, and the level of serum UA, BUN, Cr, TC, LDL-c, ATL, AST raised significantly meanwhile TG reduced. At the 4th week, the serum UA in high purine diet group did not raise, and the serum XOD raised obviously while ADA did not; the serum UA in lipid emulsion group was higher significantly, and the serum XOD and ADA raised while Cua/Ccr reduced obviously. At the 6th weeks, the serum UA in both the high purine diet group and lipid emulsion group raised obviously. After stopping modeling, the serum UA in lipid emulsion group still maintained a high level at the 2nd week and back to the normal level at the 4th week. Compared with high purine diet, the hyperuricemia model induced by lipid emulsion forms earlierand more stable. It maybe has great value to study the pharmacodynamics of traditional Chinese medicine treatment to hyperuricemia disease. Its mechanism may be related to increasing XOD and ADA enzyme activity which can promote uric acid synthesis, meanwhile inhibiting of uric acid excretion.
Animals ; Diet ; adverse effects ; Disease Models, Animal ; Emulsions ; adverse effects ; metabolism ; Humans ; Hyperuricemia ; metabolism ; Lipid Metabolism ; Lipids ; chemistry ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of parenteral nutrition support with a lipid emulsion formulation (containing soybean oil, medium chain triglycerides, olive oil, and fish oil [SMOF]) in intensive care patients following major gastrointestinal surgeries.

METHODSAccording to a randomized, prospective and case-controlled design, 72 intensive care patients following major gastrointestinal surgeries between January and December, 2014 were randomized equally into SMOF group and control group to receive parenteral nutrition support with SMOF and medium or long chain lipid emulsion, respectively. Before and at 4 and 9 days after commencement of parenteral nutrition support, the patients were examined for alanine aminotransferase (ALT), total bilirubin (TBIL), albumin (propagated), C-reactive protein (CRP), interleukin 6 (IL-6), and endotoxin levels. The patients' average length of stay in intensive care unit (ICU), the days of using antibiotics, and the incidence rate of postoperative complication were recorded.

RESULTSOn day 4 postoperatively, the levels of CRP and IL-6 were significantly lower in SMOF group than in the control group (t=2.669 and 2.676, respectively; P<0.05), and on day 9, the patients in SMOF group showed significantly lower levels of ALT, TBIL, CRP and IL-6 (t=2.487, 3.497, 3.762, 2.180, respectively; P<0.05) than the control group, but ALB and endotoxin levels remained comparable between the two groups. The average length of stay in ICU and the days of using antibiotics were significantly shorter in SMOF group than in the control group (t=2.94 and 2.17, respectively; P<0.05); SMOF group showed a lower incidence of postoperative infections than the control group, but the difference was not statistically significant (χ² =1.047, P>0.05).

CONCLUSIONFor intensive care patients following major gastrointestinal surgeries, postoperative parenteral nutrition support with SMOF can effectively reduce the release of inflammatory mediators, protect important visceral functions, reduce postoperative complications, shorten the length of ICU stay, and improve the prognosis of the patients.

Alanine Transaminase ; blood ; Bilirubin ; blood ; C-Reactive Protein ; chemistry ; Critical Care ; Digestive System Surgical Procedures ; Fat Emulsions, Intravenous ; therapeutic use ; Fish Oils ; Humans ; Interleukin-6 ; blood ; Olive Oil ; Parenteral Nutrition ; Plant Oils ; Prospective Studies ; Soybean Oil ; Triglycerides