Preparation of co-spray dried cushioning agent containing stearic acid for protecting pellet coatings when compressed.

This study investigated the applicability of stearic acid as a co-adjuvant in cushioning agent formulated to prevent coat damage when compressing coated pellets. The co-processed and physical blended fillers were prepared by spray drying and physically blending, respectively, with filler ingredients consisting of stearic acid, microcrystalline cellulose, fully gelatinized starch, and corn starch. Pellets containing drug were produced by coating onto non-pariels a drug layer of metformin followed by a sustained-release layer. Drug release from tablets composed of co-processed or physical blended fillers (0, 1, 5, and 10% stearic acid levels) and coated drug containing pellets were analyzed using similarity factor F2. Under the same force and the stearic acid level, co-processed fillers produced pellet containing tablets which showed higher F2 or t50 values and tensile strengths as well as lower yield pressures as compared with tablets containing physical blended fillers. It was shown that the destructive degree of pellet coating was significantly reduced after being co-processed by homogenization and the incorporation of stearic acid in the cushioning agents, as shown by the improved F2 and t50 values. In addition, disintegrate times of tablets containing co-processed agents decreased despite the hydrophobic stearic acid. In conclusion, the inclusion of stearic acid in co-processed cushioning agents was effective at protecting compacted coated pellets from compression-induced damage without compromising disintegratability. The findings could serve as a step towards resolving the technical challenges of balancing the drug release profiles, tablet tensile strength, and disintegration time of compacting coated pellets into multi-particulate-sustained release tablets.

A review of experimental research on herbal compounds in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease worldwide, leading to progressive muscle atrophy and paralysis. The limited success of conventional treatment for ALS has prompted investigations into complementary and alternative therapies. Herbal remedies provide good prospects of ALS prevention and treatment, with advantages such as multiple targets, multiple links, and few side effects. Studies in vitro and in vivo have shown that herbs have a great potential for treatment of ALS, with therapeutic effects against oxidative stress, excitatory amino acid toxicity, neuroinflammation, and calcium cytotoxicity. Active monomers or ingredients extracted from herbs are considered promising candidates for ALS. Therefore, we review recent experimental research on monomers and compounds isolated from herbal remedies for preventing and treating ALS.

[Application of factor analysis to evaluate deformation behaviors of frequently-used tablet excipients].

The present work is to investigate the correlation between physical properties and deformation behaviors of tablet excipients, and rank them according to their plastic performances during compaction. The excipients selected were compacted using Korsch XP1 after measuring their physical properties where the compression parameters for evaluating deformation behaviors were Heckle equation, compression work and elastic stretch in die. The correlations between compaction descriptors and physical parameters were analyzed by canonical correlation analysis, and factor analysis was simultaneously employed to synthetically assess deformation behaviors for all our samples. The canonical variables show that true density (Pa) correlated negatively with plastic coefficient (PL) and positively with yield pressure (YP); compression degree (Cp) correlated negatively with fast elastic stretch (FES) as well as YP and positively with PL. When factor scores were used in combination with original data, the plasticity of our samples was sorted and ranked as high (-0.56 < F' < 0.21), intermediate (-0.16 < F' < 0.36), or low (0.38 < F' < 0.84), which are in accord with plasticity rankings previously reported in literature. This study indicates factor analysis can be an approach to evaluate deformation behaviors of pharmaceutical powders.

[Discrimination of traditional Chinese medicinal materials with different tastes based on electronic tongue].

OBJECTIVE: To investigate the use of the electronic tongue in the evaluation of traditional Chinese medicinal materials with sour, bitter, sweet or salty tastes, and assess the possible application of the sensor in the evaluation of different tastes of traditional Chinese medicinal materials. METHOD: Aqueous extracts of 22 traditional Chinese medicinal materials were measured by the electronic tongue. The data collected with the tongue was evaluated for discrimination of the samples with multivariate statistical methods: principal component analysis (PCA) and discriminant factor analysis (DFA). RESULT: The electronic tongue was capable of discriminating between samples with different taste modalities and could also distinguish different samples eliciting the same basic taste. Twenty-two traditional Chinese medicinal materials could be classified into five clusters based on PCA. These differences seem to derive from the different tastes. DFA was applied to construct a model to discriminate traditional Chinese medicinal materials with different tastes. And the samples yielded about 88.2% accuracy for cross-validation. CONCLUSION: We confirmed that the electronic tongue may provide an analytical procedure for classification of the samples with respect to tastes of the traditional Chinese medicinal materials.

Characterization using LC/MS of the absorption compounds and metabolites in rat plasma after oral administration of a single or mixed decoction of Shaoyao and Gancao.

Shaoyao-Gancao decoction (SGD), a traditional Chinese formulation containing Paeoniae Radix (SY) and Glycyrrhizae Radix (GC), is commonly used to relieve abdominal pain. However, the absorption and metabolites of the characteristic constituents of the two herbs in vivo have been reported rarely. The purpose of this study was to investigate the compatibility rationality and the mechanism of the enhanced efficiency of SGD. A single or a mixed decoction (SG and S+G, respectively) was orally administered to rats. Blood samples were collected at different intervals following treatment and analyzed by liquid LC/MS. A total of fifteen ingredients (denoted as M1 to M15) were found in both rat plasma after treatment with the two decoctions. Furthermore, the proposed structures of the remained twelve ingredients were obtained except M9, M10 and M15. The quality of the ingredients in the rat plasma showed no significant difference between the two decoctions. However, the quantity of twelve ingredients differed greatly, indicating that the absorption of SG was greater than that of S+G except M7, M12 and M15. As the compositions associated with the efficacy of SG and S+G were inconsistent, the degree of the absorption of the 15 ingredients by the gastrointestinal tract were different, which caused a significantly enhanced efficacy of certain ingredients. This study presents an exploration of the mechanism behind the improved efficacy of individual components in traditional Chinese medicine therapies through combination with other components.

Comparative pharmacokinetics of senkyunolide I in a rat model of migraine versus normal controls.

Senkyunolide I is an active ingredient of Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. In the present paper, we describe the isolation and elucidation of senkyunolide I from the ethanol extract of Rhizoma Chuanxiong and its pharmacokinetic behavior after intravenous and oral administration to normal and migrainous rats. After intravenous administration, senkyunolide I was rapidly distributed (V ( z )/F 2.07 ± 0.43 L/kg) and eliminated from the plasma (CL( z ) 2.56 ± 0.29 L/h/kg and t (1/2z ) 0.56 ± 0.13 h). After administration orally to normal rats at two dosages (20 and 72 mg/kg), the pharmacokinetic parameters of senkyunolide I were as follows: T (max) 0.25 ± 0.06 and 0.38 ± 0.11 h, C (max) 5,236.3 ± 802.8 and 22,071.9 ± 3,456.1 mg/L, Area under the curve(AUC)((0-t)) 5,217.5 ± 1,029.5 and 21,480.2 ± 3,003.1 µg h/L, respectively. Its oral absolute bioavailability at the two dosages was 67.2 and 76.9%, respectively. Intriguingly, migraine caused some significant changes in its pharmacokinetic parameter. For example, when compared with its pharmacokinetic behavior in normal rats at the two dosages, on average, its clearance decreased by 68% and volume of distribution increased by 342% in migrainous rats, both of which contributed to its several-fold increase in t (1/2z) and AUC. C (max) and AUC of senkyunolide I increased almost proportionally with dose between 20 and 72 mg/kg and the pharmacokinetics fit linear kinetic feature. The pharmacokinetic parameters of senkyunolide I were significantly different in normal and migrainous rats, which should be taken into account during the design of a clinical dosage regimen for senkyunolide I.

Pharmacokinetics of characteristic effective ingredients from individual and combination Shaoyao and Gancao treatment in rats using HPLC fingerprinting.

Shaoyao-Gancao decoction, a traditional Chinese formulation composed of Paeoniae Radix and Glycyrrhizae Radix, is commonly used to relieve abdominal pain. In this paper, the compatibility rationality of this decoction was investigated. Shaoyao-Gancao decoction, Shaoyao decoction and Gancao decoction were orally administered to rats, respectively. Blood samples were collected at pre-determined times after administration and analyzed by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters of characteristic peaks were analyzed and the statistical significance of the obtained parameters was determined. Paeoniflorin (12.0 min) and compounds at retention times of 4.7 and 5.2 min were all significantly higher in the Shaoyao-Gancao decoction than in the Shaoyao decoction (P < 0.05). In contrast, in the Gancao decoction, the compound at a retention time of 14.6 min was significantly lower than in the Shaoyao-Gancao decoction (P < 0.01). However, the compounds at retention times of 17.1 and 18.1 min were significantly higher in the Gancao decoction than in the Shaoyao-Gancao decoction (P < 0.05). These results indicate that poor compatibility of the compounds in the Shaoyao-Gancao decoction could result in poor absorption. The compatibility of the component compounds of the Shaoyao-Gancao decoction was revealed in the pharmacokinetic characteristics of the decoction. Generally, the absorption of Shaoyao components was increased in the Shaoyao-Gancao decoction, while the absorption of Gancao components was time dependent. In the Shaoyao-Gancao decoction, the increased absorption of some Shaoyao components may be related to a reduction in absorption of some Gancao components.

Comparison of the effects of fungal endophyte Gilmaniella sp. and its elicitor on Atractylodes lancea plantlets.

The effects of the endophytic fungus Gilmaniella sp. and its elicitor on the defense and metabolic responses of host plants Atractylodes lancea were investigated, in order to understand how to utilize endophytic fungi and their elicitor resources better. The results showed that the promotion effect of the fungus on the growth of host plantlets was much better than that of its elicitor. Both fungus and elicitor enhanced defense-related enzyme activities. In fungus-inoculated groups, phenylalanine ammonia lyase and polyphenol oxidase activities increased slowly, and reached a maximum level during the later stages, whereas peroxidase activity peaked in the first few days. Additionally, the activities of chitinase and ß-1,3-glucanase were significantly higher than those of the control plants. In elicitor-treated groups, however, most of the enzymes were activated during the early stage, and their highest levels were generally lower than those of the fungus-inoculated groups. Compared with the elicitor, fungal infection improved the photosynthetic rate of the host, and increased carbohydrate levels as well as chlorophyll content in host leaves. The total content of the four main components of volatile oil was also increased in elicitor-treated groups, but there was no particular pattern in this increase. Meanwhile, in the fungus-inoculated groups, the content of atractylone significantly increased with time, while the content of ß-eudesmol decreased. These results indicated that fungal elicitor could substantially improve the total content of volatile oil, while the fungus could more effectively enhance the quality of herbal medicines.

[Characterization of flowability of pharmaceutical powders based on multivariate analysis method].

The main methods of characterizing the flowability of pharmaceutical powders include repose angle method, HR method, Carr's index method, Jenike flow function method, fractal dimension method, and mass flow rate method, etc. Regarding powders with different flowabilities as the research subject, comprehensive features of pharmaceutical materials were investigated and characterized. The multivariate analysis method was employed to evaluate and analyze flowability values of the tested pharmaceutical materials. Comparing with the method of the mass flow rate, it was feasible to use multivariate analysis method to evaluate the flowability of powders. Simultaneously, the flowability of pharmaceutical materials could be ranked and definitely quantified, and critical values be determined according to the actual production, which has promoted the previous methods dependent only on the single parameter, i.e. repose angle and compression degree methods. A relatively objective standard method of evaluating flowability of powders is formed.

[Multivariate analysis of relationships between material properties and hygroscopicity of Chinese medicine raw materials].

Material properties and hygroscopicity were determined. Principal component analysis and partial least squares regression were applied to evaluate relationships between material properties and hygroscopicity of Chinese medicine raw materials. The results showed that hygroscopicity was correlated with water content, particle size distribution, water soluble characteristic and cohesion. Balanced moisture content was positively correlated with water content, particle size distribution, water soluble characteristic and cohesion. Moisture absorption velocity was negatively correlated with particle size distribution, protruding degree and positively correlated with water soluble characteristic and cohesion. Moisture absorption acceleration was positively correlated with water content, particle size distribution and negatively correlated with water soluble characteristic and cohesion. Hygroscopicity of Chinese medicine raw materials is interpreted in terms of physics.

[Pharmacokinetics of a long-circulating PEGylated Radix Ophiopogonis polysaccharide].

The pharmacokinetics of a long-circulating PEGylated Radix Ophiopogonis polysaccharide (ROP) was investigated in rats following i.v. or s.c. administration at three dose levels (9, 20, 50 mg x kg(-1)). A moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG was chosen to produce PEGylate ROP. The grafting degree of the prepared conjugate was 1.03, and the molecular mass of mPEG used was 20 kDa. High-performance gel permeation chromatorgraphy with fluorescein isothiocyanate prelabeling was established to determine levels of the conjugate in plasma. The results showed that the elimination half-life of the conjugate following s.c. administration was basically identical to that after iv administration. An accurate linear correlation was observed between administration doses and areas under the curve of plasma conjugate level vs. time profile, regardless of the administration route. The absolute bioavailability of the conjugate following sc administration was approximately 56%, and the mean in vivo residence time was 52.1 h, increased 2.4 times compared to those of iv administration. In general, linear pharmacokinetics was observed for the conjugate within the dose range studied, and sc should be a promising administration route for the conjugate.

[Pharmacokinetics study on characteristic ingredients of different-dose herbs of shaoyao-gancao decoction].

The paper is to report the observation of pharmacokinetic changes of the characteristic ingredients in the combinations of different-dose herbs of Shaoyao-Gancao decoction. After the establishment of HPLC analytical method of plasma effective constituents, rats were orally administered with different-dose herbs of Shaoyao-Gancao decoction. Blood samples at different times after administering these decoctions were collected, and then were analyzed by HPLC fingerprints technology. Pharmacokinetic parameters of characteristic peaks were analyzed by SPSS 15.0 software and DAS 2.0. At last, we looked for the correlation of those pharmacokinetic parameters and the dosage of Gancao. The best dose of Shaoyao-Gancao decoction was at the ratio of 4 to 4, which was consistent with the dose commonly used in ancient times. The absorption of characteristic peaks from Shaoyao-Gancao decoction was related with the dosage of Gancao, and there existed interaction between each characteristic ingredients. There existed the right dose-ratio of Shaoyao and Gancao to get the best effect. The absorptions of effective constitutents were mutual waxing and waning in order to increase biological effects together. It's demonstrated the compatibility connotation at a right dose-ratio of Shaoyao-Gancao decoction through the angle of pharmacokinetics.

A polysaccharide, MDG-1, induces S1P1 and bFGF expression and augments survival and angiogenesis in the ischemic heart.

Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed its beneficial properties, but not the mechanism of action. Herein, we investigate the anti-ischemic properties of a water-soluble beta-d-fructan (MDG-1) from Ophiopogon japonicus, and assess the cytoprotective and proangiogenic effects of MDG-1. MDG-1 protects cardiomyocyte and microvascular endothelial cells (HMEC-1) against oxygen glucose deprivation (OGD)-induced cell death, as well as protect myocardial cells from ischemia-induced death occurring after coronary artery ligation in rats. Meanwhile, MDG-1 stimulates the differentiation of HMEC-1 cells into capillary-like structures in vitro and functions as a chemoattractant in migration assays, and promotes neovascularization in ischemic myocardium. In addition, MDG-1 upregulates sphingosine kinase 1 and sphingosine-1-phosphate (S1P) receptor 1 expression. Both MDG-1 and S1P induce basic fibroblast growth factor (bFGF) expression in HMEC-1 cells. Further study revealed that both MDG-1 and S1P induce Akt and ERK phosphorylation in a dose- and time-dependent manner, an effect that is attenuated by pre-treatment with either the Akt inhibitor wortmannin or the ERK inhibitor PD98059, and MDG-1 can also induce eNOS phosphorylation and increases in production of NO. These data indicate that MDG-1 presented remarkable anti-ischemic activity and protects cardiomyocyte and HMEC-1 cells from ischemia-induced cell damage by inducing S1P1 and bFGF cytoprotective and proangiogenic effects via the S1P/bFGF/Akt/ERK/eNOS signaling pathway.

Influence of sulfation on anti-myocardial ischemic activity of Ophiopogon japonicus polysaccharide.

Ophiopogon japonicus polysaccharide (FOJ-5) from Radix ophiopogonis has shown anti-myocardial ischemic action in vitro and in vivo in our previous studies. In order to clarify the influence of chemical modifications on the action, a series of sulfated FOJ-5 (FOJ-5-S) with different substitution degrees were prepared and the anti-myocardial ischemic action of the natural FOJ-5 and the FOJ-5-S were studied in vitro and in vivo. Langendorff isolated rat hearts and acute myocardial ischemic rats induced by isoprenaline were employed as myocardial ischemic models in our experiments. The amplitude and frequency of cardiac contraction, coronary blood flow at different time points after ischemia/reperfusion were measured in vitro. The ST segment shift in electrocardiogram and lactate dehydrogenase level in blood plasma were observed on the in vivo model. The results indicated that FOJ-5 and FOJ-5-S had the anti-myocardial ischemic action compared with non-treated vehicle groups. Furthermore, it was found that FOJ-5-S had significant action on the in vivo model compared with FOJ-5 (P < 0.05). And the obtained results from the further study also indicated that only when the degree of substitution was in a certain range, the FOJ-5-S had excellent anti-myocardial ischemic activity.

[Study on the preparation of sustained-release pellets containing active components from Gastrodia elata by fluid-bed coating].

OBJECTIVE: To study the formulation of sustained-release pellets containing active components from Gastrodia elata by coating in the fluid-bed. METHODS: The sustained-release pellets were prepared with Eudragit RS 100. The formulation was optimized by the direct comparison. Then their properties were evaluated. RESULTS: The pellets presented the perfect sphericity and narrow diameter distribution and the curve of their cumulative drug release was in accord with Higuchi equation. CONCLUSION: The pellets have sustained-release effect in 12 hours.

Anthraquinone pharmacokinetics in Xiexin decoction and the different combinations of its constituent herbs.

Xiexin decoction (XXD), a classical pyretolytic formulation, is composed of Rhei rhizoma (DH) Radix scutellaria (HQ) and Coptis chinensis (HL), and commonly used in the clinical setting. The aim of this study was to investigate the pharmacokinetic differences between the five anthraquinones it contains (aloe-emodin, rhein, emodin, chrysophanol and physcion) in rats after the oral administration of XXD and after the administration of the different combinations of its constituent herbs. Twenty rats were divided into four groups and randomly administered one of the four extracts: DH, DH and HQ (DH-HQ), DH and HL (DH-HL), and XXD (DH-HQ-HL) via intragastric gavage (i.g.). Anthraquinone concentrations in the plasma were determined by an HPLC technique. Pharmacokinetic parameters were calculated from the plasma concentration time data. Compared with DH alone, the DH-HL combination showed maximum plasma concentration decreased (Cmax) and area under curve (AUC) for the values anthraquinones, and a prolonged eliminatun half life (T(1/2)) for rhein, while the DH-HQ combination showed a decrease Cmax for rein and a prolonged T(1/2) for aloe-emodin and physcion. Finally, XXD (DH-HQ-HL) administration resulted in an increased AUC for all five anthraquinones compared to DH-HL, and increased the total of AUC for rhein, emodin, chrysophanol and physcion compared to DH alone. These results showed that the oral bioavailability of the five anthraquinones was significantly decreased by combining DH with HL, whereas HQ increased the amounts of absorbed anthraquinones (except for aloe-emodin), and weakened the effect of HL which inhibited the absorption of anthraquinones.

[Advances in research on in vivo-in vitro correlation of sustained-release oral dosage forms in traditional Chinese medicine].

In this review, methods for testing in vitro release rate of sustained release preparations of traditional Chinese medicine (TCM) and in vivo-in vitro correlation were introduced. Studies indicated that a good correlation between in vivo and in vitro release can be obtained by establishing methods of in vitro release and it is important for the development of sustained release drug delivery system in TCM.

[Enriching of total flavonoids from Herba Leonuri with polyamide and macroporous resin].

OBJECTIVE: To study the enriching method of total flavonoid from Herba Leonuri with polyamide and macroporous resin. METHOD: Seven enriching and purifying methods were compared with the yield and purity as indexes. The method of enriching with polyamide and macroporous resin was confirmed and the process of purifying was determined by orthogonal design. RESULT: D101 resin is packed by wet method, the ratio of diameter to height is 1:7. After mixed with the extract liquids, the weight of wet resin increased to 3 times of the dry resin. Evaporated the wet resin to dryness, mixed well with a little of 95% ethanol and dry polyamide powder, evaporated them to dryness again. Elute with deionized water until the effluent being colourless, then loaded it on the macroporous adsorptive resin, elute with 50% ethanol, the volume of effluents was collected to 7 times of the column volume. The purity of total flavonoids reached to 23%, while the diversion rate from raw Herba Leonuri was to 69%. CONCLUSION: The process is simple and convenient, and the regeneration of resin is easy, which has a good application foreground.

[Study on fingerprints correlated with pharmacodynamic of Paeonia lacliflora and Glycyrrhiza uralensis effective compounds].

OBJECTIVE: To study the spasmolysisy activity constituents of the Radix Paeoniae alba and Radix et Rhizoma compound. METHOD: The three effective compounds of Radix Paeoniae and Radix et Rhizoma were arrayed to eight groups by orthogonal design rat, serum samples were collected after administered in these groups, and these serum samples were used to carry out the experiments of serum pharmacology of spasmolysis. The inhibition ratios were assigned as pharmacodynamic variable X, the areas of characteristic peaks on HPLC fingerprints were assigned as variable Y, and the correlation of X and Y was studied in order to research the activity spasmolysisy compounds of effective constituents. Serum samples were analyzed by HPLC-ESI-MS/MS. RESULT: The correlation of fingerprints and pharmacology showed that four compounds were the main spasmolysisy activity compounds. The correlation parameter was greater than >0.4, whose value were 0.774, 0.678, 0.566 and 0.472 respectively, and their retention times were 8.03, 51.7, 54.59 and 72.43 min respectively. They were metabolites of effective compounds. CONCLUSION: This study makes a valid approach for understanding the material foundation of TCM by establishing the correlation of fingerprints and pharmacology of activity compounds in vivo.

[Advances in research on drug release mechanisms and modes of thermosensitive gel].

Thermosensitive gel with the property of LCST (Lower Critical Solution Temperature) was studied as a hot spot these years for it can be used as one supportor of drug controlled release system which can release drug at right point, right time and right quantity. With further reseaches and applications of thermosensitive gel, the modes and mechanisms of it were discovered and poited out, drug release models were also established step by step. Resesrches on drug release mechanisms and modes of thermosensitive gel will make it applied better in fields of medicine and biology.