Hong Yl

Effect and mechanism of senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong

Objective  To evaluate the analgesic and anti‐migraine activities of senkyunolide I from Ligusticum chuanxiong.

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. Copyright

Composite particles based on particle engineering for direct compaction

Direct compaction (DC) is the preferred method for tablet production. However, only a minority of the active pharmaceutical ingredients (APIs) can be truly manufactured into tablets by DC so far due to that most of APIs lack sufficient functional properties required for DC. Particle engineering with co-processing provides a promising way to obtain various composite API and/or excipient particles with markedly improved functional properties, which makes successful tableting of them by DC possible. This review, as an informative update and supplement, covers the improvement of functional properties of composite API and/or excipient particles via co-processing based on recent developments and researches in the area of particle engineering for DC. The improved functionality of co-processed particles and corresponding mechanisms were summarized and discussed from the perspective of structure characteristics (Crystal level and Particle level) as the properties of particles are markedly affected by their structure.

Identification of senkyunolide I metabolites in rats using ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry

Ligusticum chuanxiong Hort. (Umbelliferae) has been widely prescribed to treat cardiovascular disease in China for centuries. Senkyunolide I is one of the major bioactive components in L. chuanxiong, which shows pharmacological activities against migraines and oxidative damage. In this paper, ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) was applied for the rapid analysis of senkyunolide I metabolites in rats after its intravenous administration. The non-metabolized parent compound and eighteen metabolites from drug-treated samples in rat plasma, urine and bile were identified. Our analysis indicated that methylation, hydration, epoxidation, glucuronidation and glutathione conjugation were the major pathways of senkyunolide I metabolism in vivo. This study provides important information regarding the metabolism of senkyunolide I, which will be helpful for understanding its mechanism of action. Furthermore, this work demonstrates the potential of using UPLC/Q-TOF-MS for the rapid and reliable characterization of the metabolites of natural products.

A protocol for the classification of wet mass in extrusion–spheronization

In this study, a structured protocol for the classification of wet mass in extrusion-spheronization was developed to predict formation and pellet quality. The wet masses of 120 formulae were prepared taking microcrystalline celluloses as pelletization aid and lactose, hydroxypropyl methylcellulose grades, herbal medicines as model drugs. Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were tested, respectively, using a texture analyzer. Particles were produced by spheronization process, and the quality of spherical pellets was also evaluated. Data were analyzed by principal component analysis, factor analysis, and classification analysis. The wet masses could be classified into five groups taking the ratio of hardness to springiness (Ha/Sp) as the first classification index and chewiness, resilience as the second and the third classification index. The wet masses of different classification could correspondingly form the different shapes. So, a new protocol could be devised, for example, if the range of Ha/Sp of the wet masses was 30,992-47,689 g, at the same time, the value of chewiness was less than 4842, and the value of resilience was no more than 0.139; it would form spherical pellets under the experimental condition. These results demonstrate that the proposed protocol could be a valuable asset in a formulation development project to assess the physical properties of wet masses and to predict formation and pellet quality. So, the tedious and expensive pre-production (pre-formulation and optimization) work could be considerably reduced.

PEGylation for drug delivery to ischemic myocardium: Pharmacokinetics and cardiac distribution of poly(ethylene glycol)s in mice with normal and ischemic myocardium

PEGylation now plays an important role in drug delivery and is considered as the method of choice for improving the pharmacokinetics and stability of parenteral agents. However, its application in treating cardiac diseases is still limited. To guide the design of PEGylation for drug delivery to ischemic myocardium, the effects of the molecular weight of PEG and the myocardial ischemic conditions on PEG levels in plasma and myocardium were studied in this work following intravenous administration of fluorescein isothiocyanate-labeled 20- and 40-kDa mPEGs to mice with normal and ischemic myocardium. The results show that myocardial ischemia caused some consistent changes in pharmacokinetic parameters of mPEGs. Due to the enhanced permeability and retention (EPR) effect caused by ischemia, the distribution of 20- and 40-kDa mPEGs in ischemic hearts was approximately 1.47- and 1.92-fold higher than that in normal hearts, respectively. Under the same heart condition (either normal or ischemic), the cardiac AUC(0.5-24h)s of the two mPEGs were comparable, although their plasma AUCs differed by nearly 4-fold; however, a smoother cardiac level-time profile was achieved by 40-kDa mPEG. This study addressed the relative importance of the EPR effect of ischemic zones and the molecular size of PEG in cardiac drug delivery, which is believed to be helpful for macromolecular drug design.

Hydroxypropyl Methylcellulose Reduces Particle Adhesion and Improves Recovery of Herbal Extracts During Spray Drying of Chinese Herbal Medicines

The effectiveness of hydroxypropyl methylcellulose (HPMC) as an anti-adherent during spray drying of traditional Chinese herbal extracts was explored. A small amount of HPMC (minimum concentration 8%) was sufficient to overcome problematic particle adhesion, whereas a large amount of maltodextrin (50%) was required for the same effect. HPMC exerted a strong anti-adhesive effect that was independent of the type of HPMC, raw materials used, and the process used to synthesize HPMC. The anti-adhesion mechanism was studied through an analysis of the surface tension of the prepared solutions before spray drying, the glass transition temperature (T g ), and X-ray photoelectron spectroscopy (XPS) of spray-dried powders. The T g of powders containing more than 8% HPMC was approximately 40°C and did not increase linearly with the HPMC concentration. The surface tension of Crataegi fructus extract was 54.1 ± 0.2 mN/m and further decreased to 46.6 ± 0.2 mN/m upon addition of HPMC to 24%. When the concentration of HPMC increased to 8%, potassium could not be detected on the surface of dried powders by XPS. These results suggest that modification of the surface properties of sprayed droplets/particles by HPMC increased the HPMC surface coverage of the particles and reduced adhesion during spray drying.

Recent pharmaceutical evidence on the compatibility rationality of traditional Chinese medicine

ETHNOPHARMACOLOGICAL RELEVANCE Chinese herbs have been used in China for thousands of years and are also becoming popular in Western medicine. Formulae of traditional Chinese medicine (TCM), which contain two or more herbs, can often obtain better curative efficacies and fewer side effects than single herbs. Though there are many reports on pharmaceutics, pharmacokinetics, and pharmacodynamics of TCM, there remains a serious lack of summarization and systemic analyses of these reported data to help uncover the compatibility rationale of TCM. This review therefore aims to provide such an overview mainly based on the reports published in the last decade. It could be served as an informative reference for researchers interested in compound prescriptions and holistic therapies. MATERIALS AND METHODS Relevant information was collected from various resources, including books on Chinese herbs, China Knowledge Resource Integrated (CNKI), and international databases, such as Web of Science, Scopus, and PubMed. RESULTS Thirty-six relevant TCM formulae were collected to illustrate the compatibility rationality of TCM from the perspective of pharmaceutics, pharmacokinetics, and/or pharmacodynamics. CONCLUSIONS Compatibility is a key characteristic of multi-herb prescriptions. It often results in the change of the therapeutic material basis and, thus, produces the effect of reducing toxicity and/or increasing curative efficacy.

Hydrophobic mixed solvent induced PLGA-based in situ forming systems for smooth long-lasting delivery of Radix Ophiopogonis polysaccharide in rats

To overcome the deficient sustained release of bioactive Radix Ophiopogonis polysaccharide (ROP) from hydrophilic solvent-induced PLGA-based in situ forming systems (ISFSs), hydrophobic mixed solvent-induced ISFSs were investigated, including the factors affecting drug release and the anti-myocardial ischemic activity of a representative formulation. The initial release was reduced by 3.7–8.0 times and the plasma level was significantly prolonged from 4 days to 10–15 days as the hydrophilic N-methyl-2-pyrrolidone (NMP) was replaced by the hydrophobic mixed solvent consisting of 90% benzyl benzoate (BB) and 10% co-solvent (benzyl alcohol, triacetin, or NMP). The effect of 10% co-solvent on the phase inversion rate, depot morphology, and ROP release was unexpectedly high, with NMP surprisingly being optimal although having much higher hydrophilicity. Further studies indicated that the release behaviour could be tailored by changing the ratio of BB to NMP, PLGA molecular weight, and PLGA concentration. Linear reductions in Cmax and AUC0–12 h were observed with the increase of the ratio (7 : 3 to 9 : 1), PLGA MW (20 to 40 kDa), and PLGA level (20% to 40%), respectively. Moreover, it is possible to achieve nearly zero-order release by different formulation combinations. The bioactivity data suggested that thanks to sustained stable release of ROP, the ISFS studied showed an obvious advantage over aqueous solution in the treatment of myocardial ischemia. Therefore, ISFSs with hydrophobic mixed solvents like BB/NMP appear to be promising and suitable for smooth long-lasting release of herb polysaccharides with low oral bioavailability and short plasma half-life, like ROP.

Design and pharmaceutical applications of porous particles

Porous particles (PPs) are a novel kind of carrier with a large surface area, high porosity, stable uniform porous structure, tunable pore sizes with narrow distribution, and well defined surface properties. There are many methods for preparing PPs, mainly including using porogens or templating agents to form pores, self-forming pores by particle matrices without any pore-forming agents, and chemical synthesis. In this review, reports on various PPs are collected, which are applied in various fields of medicine for many purposes, such as improvement of dissolution of poorly soluble drugs, development of novel drug delivery systems, and improvement of the functional properties of drug-loaded particles. In general, these functions of PPs are closely related to their fundamental particle and pore properties, such as morphology, size, surface property, surface area, and porosity. The reasonable application of PPs has markedly facilitated the development of pharmaceutics and the number of published reports has increased progressively from year to year. However, there remains a serious deficiency of summarization and systematic analysis of these reports. Therefore, this review aims to provide a comprehensive and relevant overview on the design and pharmaceutical applications of PPs, which can serve as an informative reference for interested readers.