Stability and drug dissolution evaluation of Qingkailing soft/hard capsules based on multi-component quantification and fingerprint pattern statistical analysis

Purpose: To carry out a post-marketing evaluation of the stability and drug dissolution of Qingkailing soft/hard capsules.Methods: High performance liquid chromatography with diode array detection (HPLC-DAD) method was developed for the determination of three key ingredients (chlorogenic acid, geniposide and baicalin) and fingerprints of QKL soft/hard capsules. Stability tests were carried out based on long-term testing. The drug release profile of Qingkailing soft and hard capsules were studied using semi-bionic incubation experiments.Results: The linearity, precision, stability, repeatability and recovery of HPLC and fingerprint all met the requirements of CFDA. Stability data from long-term studies showed that within 6 months the contents of the three key ingredients in both soft and hard capsules remained > 90 %. However, fingerprint pattern statistical analysis showed that the soft capsule is more stable than the hard capsule. Furthermore, the key ingredients of the hard capsule dissolved much faster (p < 0.05) than from the soft capsule. The level of dissolved drug of hard capsule is about 4 times the rate of soft capsule, after a 4-h incubation in gastric lavage fluid. In intestinal lavage fluid, more than 90 % of chlorogenic acid, geniposide and baicalin of hard capsule were dissolved in 2 h, while the soft capsule displayed a 12 h sustained release. Fingerprint pattern statistical analysis also showed that most of the components of soft capsule dissolved after 8 h.Conclusion: Compared with the hard capsule, Qingkailing soft capsule has certain advantages in stability and drug dissolution, which may affect the biopharmaceutics and the clinical effects of the drug.Keywords: Qingkailing capsule, Chlorogenic acid, Geniposide, Baicalin, Fingerprint, Sustained release, Principal component analysi

Genome-wide Association Study (GWAS) of mesocotyl elongation based on re-sequencing approach in rice

Annotation of candidate genes anchored by associated SNPs. (XLSX 34 kb

Carnosic Acid Mitigates Early Brain Injury After Subarachnoid Hemorrhage: Possible Involvement of the SIRT1/p66shc Signaling Pathway

Carnosic acid (CA) has been reported to exhibit a variety of bioactivities including antioxidation, neuroprotection, and anti-inflammation; however, the impact of CA on subarachnoid hemorrhage (SAH) has never been elucidated. The current study was undertaken to explore the role of CA in early brain injury (EBI) secondary to SAH and the underlying mechanisms. Adult male Sprague-Dawley rats were perforated to mimic a clinical aneurysm with SAH. CA or vehicle was administered intravenously immediately after the SAH occurred. Mortality, SAH grade, neurologic function scores, brain water content, Evans blue extravasation, and the levels of reactive oxygen species (ROS) levels in the ipsilateral cortex were determined 24 h after the SAH occurred. Western blot, immunofluorescence, Fluoro-Jade C (FJC) and TUNEL staining were also performed. Our results showed that CA decreased ROS levels, alleviated brain edema and blood-brain barrier permeability, reduced neuronal cell death, and promoted neurologic function improvement. To probe into the potential mechanisms. We showed that CA increased SIRT1, MnSOD, and Bcl-2 expression, as well as decreased p66shc, Bax, and cleaved caspase-3 expression. Interestingly, sirtinol, a selective inhibitor of SIRT1, abolished the anti-apoptotic effects of CA. Taken together, these data revealed that CA has a neuroprotective role in EBI secondary to SAH. The potential mechanism may involve suppression of neuronal apoptosis through the SIRT1/p66shc signaling pathway. CA may provide a promising therapeutic regimen for management of SAH

Amplitude analysis of Ds+→π+π−π+D_s^{+} \rightarrow \pi^{+} \pi^{-} \pi^{+}

Utilizing the data set corresponding to an integrated luminosity of $3.19$ fb$^{-1}$ collected by the BESIII detector at a center-of-mass energy of 4.178 GeV, we perform an amplitude analysis of the $D_s^+\to\pi^+\pi^-\pi^+$ decay. The sample contains 13,797 candidates with a signal purity of $\sim$80%. The amplitude and phase of the contributing $\pi\pi$ ${\cal S}$ wave are measured based on a quasi-model-independent approach, along with the amplitudes and phases of the ${\cal P}$ and ${\cal D}$ waves parametrized by Breit-Wigner models. The fit fractions of different intermediate decay channels are also reported.Comment: 14 pages, 6 figure

Search for Λˉ\bar{\Lambda}-Λ\Lambda oscillations in the decay J/ψ→pK−Λˉ+c.c.J/\psi \to p K^- \bar{\Lambda}+c.c.

We report the first search for $\bar\Lambda$--$\Lambda$ oscillations in the decay $J/\psi \to p K^- \bar{\Lambda} + c.c.$ by analyzing $1.31\times10^9$ $J/\psi$ events accumulated with the BESIII detector at the BEPCII collider. The $J/\psi$ events are produced using $e^+e^-$ collisions at a center of mass energy $\sqrt{s}= 3.097$~GeV. No evidence for hyperon oscillations is observed. The upper limit for the oscillation rate of $\bar\Lambda$ to $\Lambda$ hyperons is determined to be $\mathcal{P}(\Lambda)=\frac{\mathcal{B}(J/\psi\to pK^-\Lambda+c.c.)}{\mathcal{B}(J/\psi\to pK^-\bar\Lambda+c.c.)}<4.4\times10^{-6}$ corresponding to an oscillation parameter $\delta m_{\Lambda\bar\Lambda}$ of less than $3.8\times10^{-18}$~GeV at the 90\% confidence level.Comment: 7 pages, 1 figur

Measurements of the absolute branching fractions of D0(+)→KKˉππD^{0(+)}\to K\bar K\pi\pi decays

Based on 2.93~fb$^{-1}$ $e^+e^-$ collision data taken at center-of-mass energy of 3.773 GeV by the BESIII detector, we report the measurements of the absolute branching fractions of $D^0\to K^+K^-\pi^0\pi^0$, $D^0\to K^0_SK^0_S\pi^+\pi^-$, $D^0\to K^0_SK^-\pi^+\pi^0$, $D^0\to K^0_SK^+\pi^-\pi^0$, $D^+\to K^+K^-\pi^+\pi^0$, $D^+\to K^0_SK^+\pi^0\pi^0$, $D^+\to K^0_SK^-\pi^+\pi^+$, $D^+\to K^0_SK^+\pi^+\pi^-$, and $D^+\to K^0_SK^0_S\pi^+\pi^0$. The decays $D^0\to K^+K^-\pi^0\pi^0$, $D^0\to K^0_SK^-\pi^+\pi^0$, $D^0\to K^0_SK^+\pi^-\pi^0$, $D^+\to K^0_SK^0_S\pi^+\pi^0$, and $D^+\to K^0_SK^+\pi^0\pi^0$ are observed for the first time. The branching fractions of the decays $D^0\to K^0_SK^0_S\pi^+\pi^-$, $D^+\to K^+K^-\pi^+\pi^0$, $D^+\to K^0_SK^-\pi^+\pi^+$, and $D^+\to K^0_SK^+\pi^+\pi^-$ are measured with improved precision compared to the world-average values.Comment: 11 pages, 5 figure

Search for New Hadronic Decays of hch_c and Observation of hc→K+K−π+π−π0h_c\rightarrow K^{+}K^{-}\pi^{+}\pi^{-}\pi^{0}

Ten hadronic final states of the $h_c$ decays are investigated via the process $\psi(3686)\rightarrow \pi^0 h_c$, using a data sample of $(448.1 \pm 2.9) \times 10^6$ $\psi(3686)$ events collected with the BESIII detector. The decay channel $h_c\rightarrow K^{+}K^{-}\pi^{+}\pi^{-}\pi^{0}$ is observed for the first time with a significance of $6.0 \sigma$. The corresponding branching fraction is determined to be $\mathcal{B}(h_c\rightarrow K^{+}K^{-}\pi^{+}\pi^{-}\pi^{0}) =(3.3 \pm 0.6 \pm 0.6)\times 10^{-3}$ (the first uncertainty is statistical and the second systematical). Evidence for the decays $h_c\rightarrow \pi^{+} \pi^{-} \pi^{0} \eta$ and $h_c\rightarrow K^{0}_{S}K^{\pm}\pi^{\mp}\pi^{+}\pi^{-}$ is found with a significance of $3.6 \sigma$ and $3.8 \sigma$, respectively. The corresponding branching fractions (and upper limits) are obtained to be $\mathcal{B}(h_c\rightarrow \pi^{+} \pi^{-} \pi^{0} \eta ) =(7.2 \pm 1.8 \pm 1.3)\times 10^{-3}$ $(< 1.8 \times 10^{-2})$ and $\mathcal{B}(h_c\rightarrow K^{0}_{S}K^{\pm}\pi^{\mp}\pi^{+}\pi^{-}) =(2.8 \pm 0.9 \pm 0.5)\times 10^{-3}$ $(<4.7\times 10^{-3})$. Upper limits on the branching fractions for the final states $h_c \rightarrow K^{+}K^{-}\pi^{0}$, $K^{+}K^{-}\eta$, $K^{+}K^{-}\pi^{+}\pi^{-}\eta$, $2(K^{+}K^{-})\pi^{0}$, $K^{+}K^{-}\pi^{0}\eta$, $K^{0}_{S}K^{\pm}\pi^{\mp}$, and $p\bar{p}\pi^{0}\pi^{0}$ are determined at a confidence level of 90\%.Comment: 10 pages, 2 figure

Measurement of the branching fraction of and search for a CP-violating asymmetry in η′→π+π−e+e− at BESIII

The rare decay η′→π+π-e+e- is studied using a sample of 1.3×109 J/ψ events collected with the BESIII detector at BEPCII in 2009 and 2012. The branching fraction is measured with improved precision to be (2.42±0.05stat±0.08syst)×10-3. Due to the inclusion of new data, this result supersedes the last BESIII result on this branching fraction. In addition, the CP-violating asymmetry in the angle between the decay planes of the π+π - pair and the e+e - pair is investigated. A measurable value would indicate physics beyond the standard model; the result is ACP=(2.9±3.7stat±1.1syst)%, which is consistent with the standard model expectation of no CP-violation. The precision is comparable to the asymmetry measurement in the KL0→π+π-e+e- decay where the observed (14±2)% effect is driven by a standard model mechanism