PURPOSE: To predict Caco-2 permeability is a valuable target for pharmaceutical research. Most of the Caco-2 prediction models are based on commercial or special software which limited their practical value. This study represents the relationship between Caco-2 permeability and molecular descriptors totally based on open source software. METHODS: The Caco-2 prediction model was constructed based on descriptors generated by open source software Chemistry Development Kit (CDK) and a support vector machine (SVM) method. Number of H-bond donors and three molecular surface area descriptors constructed the prediction model. RESULTS: The correlation coefficients (r) of the experimental and predicted Caco-2 apparent permeability for the training set and the test set were 0.88 and 0.85, respectively. CONCLUSIONS: The results suggest that the SVM method is effective for predicting Caco-2 permeability. Membrane permeability of compounds is determined by number of H-bond donors and molecular surface area properties.
To develop method for determining the lot-to-lot consistency of Compound Danshen drop- ping pills(CDDP).Method:Two HPLC fingerprints of the major depsides and ginsenosides in CDDP were estab- lished respectively,which constructed multiple HPLC fingerprints of CDDP.Result:The multiple HPLC fingerprints similarities of CDDP resulting from normal production process are higher than 0.95,while the similarities of CDDP resulting from abnormal production process are lower than 0.8.Conclusion:The proposed multiple HPLC finger- printing is of significant use in evaluating the lot-to-lot consistency of CDDP.
We present a random restart heuristic for the global optimization problem that is based on the principles of mutation inspired by biology, it only uses the mutation operator to search the solution space. Combining local optimization by the mutation operator and random restart method in order to increase the reliability of finding the global optimum, the new algorithm can obtain satisfactory results in limited time. The superiority of this methodology over the conventional genetic algorithm is established on some problems of optimizing complex functions.
OBJECTIVE To establish a HPLC assay for the determination of the ginsenosides R g1 and R b1 and assess the batch-to-batch consistency of Shenmai injection by chromatographic fingerprint.METHODS The chromatographic separation was performed on a Hanbang Hypersil C 18 column (5 μm,4.6 mm×250 mm).A linear gradient elution of A (50 mmol·L -1 KH 2PO 4) and B (acetonitrile-wate=80∶20) was used.The flow rate was 1 mL·min -1 .The detection wavelength was set at 202 nm,and the column temperature was 40℃.RESULTS The average recoveries of ginsenosides R g1 and R b1 were above 99% with RSD less than 1.2% .The response was linear over the range of 4.20～42.0 μg for R g1 and 3.30～33.0 μg for R b1 ,respectively.Over 30 ginsenosides were separated by the chromatographic fingerprints.CONCLUSION Combining the determination of the ginsenosides R g1 and R b1 with the comparison of chromatographic fingerprints,the quality control of Shenmai injection can be assessed.
Abstract Background Patients with ulcerative colitis (UC) who are positive for anti-neutrophil cytoplasmic antibodies(ANCA) tend to have a poor response to infliximab(IFX)1-3. We aimed to evaluate the comparative efficacy and safety of rituximab (RTX) versus IFX in moderately to severely active UC patients who are Proteinase 3-ANCA(PR3-ANCA) positive. Methods This retrospective multicentre real-world study encompassed three medical centres in Hubei, China. Patients with moderate to severely active UC who are positive for PR3-ANCA were categorized into the RTX group(100mg or 200mg by intravenous injection every 2 weeks for a total dose between 400mg and 900mg, n=12) and IFX group(5 mg/kg of intravenous at weeks 0, 2, and 6, followed by maintenance doses every 8 weeks, n=26) based on the biological therapy. The Mayo Clinic Score (MCS) was utilised to evaluate the efficacy endpoints at week 22, encompassing clinical remission(primary endpoint), clinical response, endoscopic response, endoscopic improvement, and endoscopic remission. Safety endpoints focused on opportunistic infections and drug-related adverse reactions. Inverse probability of treatment weighting(IPTW) and multifactorial logistic regression analysis(MLRS) were employed to mitigate the effects of potential confounding factors. Results The rates of clinical remission(83.33% vs. 23.08% and 93.20% vs. 25.40%), clinical response(100.00% vs. 65.38% and 100.00% vs. 64.60%), endoscopic response(100.00% vs. 34.62% and 100.00% vs. 36.06), endoscopic improvement(50.00% vs. 11.54% and 75.07% vs. 11.29%), and endoscopic remission(100.00% vs. 34.62% and 100.00% vs. 36.06%) were significantly higher in patients treated with RTX compared with those treated with IFX, both prior to and following IPTW(all P<0.05). In MLRS, RTX was associated with higher odds of achieving clinical remission at week 22 versus IFX before and after IPTW[OR(95%CI): 143.854(1.060-19521.653) and 190.499(4.147-1.000*105), all P<0.05]. In terms of safety endpoints, elevated interferon-gamma release assays(IGRAs) were noted in none of the RTX patients, and 2 IFX patients (7.69%). No patients exhibited elevated EBV-DNA, HBV-DNA, CMV-DNA, or experienced severe infections. Conclusion RTX demonstrated superior efficacy versus IFX in moderately to severely active UC patients with positive PR3-ANCA, with a comparable safety profile. References 1. Yoshida A, Matsuoka K, Ueno F, Morizane T, Endo Y, Hibi T. Serum PR3-ANCA Is a Predictor of Primary Nonresponse to Anti-TNF-α Agents in Patients with Ulcerative Colitis. Inflammatory intestinal diseases. May 2021;6(2):117-122. doi:10.1159/000515361 2. Ferrante M, Vermeire S, Katsanos KH, et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflammatory bowel diseases. Feb 2007;13(2):123-8. doi:10.1002/ibd.20054 3. Jürgens M, Laubender RP, Hartl F, et al. Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. The American journal of gastroenterology. Aug 2010;105(8):1811-9. doi:10.1038/ajg.2010.95
Objective Near-infrared (NIR) spectroscopy was used as a fast analytical technique in the ethanol reflux-extraction process of red ginseng. Methods The NIR spectra of the extracting solution of red ginseng were obtained and the reference measurements of the active constituent in the extracting solution were performed by the colorimetric method. Firstly, the interference information in the spectra was detected by orthogonal signal correction (OSC) method. Then a calibration model between NIR spectra and reference measurements was established by partial least square regression. Results The results showed that the predictive accuracy of NIR calibration model used for the determination of ginsenoside in ethanol extracting process of red ginseng was good. Conclusion NIR Spectroscopy could be applied to the fast analysis for ethanol extracting processes of red ginseng.
OBJECTIVE To study the constituents in the whole plants of Clematis puberula Hook.f. Thoms.var.ganpiniana(Levl. Van.) W.T.Wang.METHODS Column chromatography(including D101 macroporous resin,silica gel and Sephadex LH-20) and reversed-phase preparative HPLC were used to separate constituents whose structures were elucidated by ESI-MS and NMR spectral data.RESULTS Seven triterpenoid saponins were isolated,along with one lignan,and elucidated as HN saponin H(Ⅰ),huzhangoside B(Ⅱ),hederacholichiside F(Ⅲ),clematichinenoside B(Ⅳ),huzhangoside D(Ⅴ),clematichinenoside C(Ⅵ),prosapogenin CP11(Ⅶ) and clemastanin B(Ⅷ).CONCLUSION All these compounds were isolated from Clematis puberula Hook.f. Thoms.var.ganpiniana(Levl. Van.) W.T.Wang for the first time,with compound Ⅲ isolated for the first time from the genus Clematis and compound Ⅶ as a genuine saponin from plants.
OBJECTIVE To propose a new method based on Chinese medicinal chromatographic fingerprint and the contents of key constituents and apply the new method for the quality control of Chinese medicinal plant. METHODS A new blending optimization model of TCM's plant was built by a nonlinear programming method, and the optimization objective was the combination of fingerprint similarity and the relative deviation of the contents of multiple key constituents, and the optimal blending ratios was obtained by sequential quadratic programming method. RESULTS Several different batches of Danshen extracts were selected as typical research subjects, and a blend satisfied the quality criterion was obtained with the proposed method. CONCLUSION The proposed method can assure the batch-to-batch consistency of plant extracts.
OBJECTIVE To establish a RP-HPLC linear gradient elution method for simultaneously determining notoginsenoside R 1,ginsenoside Rg 1,ginsenoside Rb 1and ginsenoside Rd in Xueshuantong injection.METHODS An Agilent SB-C 18 column (4.6 mm×250 mm,5 μm) was used with the mixture of acetonitrile-phosphoric acid-water as the mobile phase in linear gradient elution.The wavelength of detection was set at 203 nm.RESULTS The response was linear over the wide concentration ranges.The average recoveries of R 1,Rg 1,Rb 1 and Rd were 103.3%,101.8%,99.6% and Rd 103.9%,respectively.RSD of the assay was not more than 1.2% (n=5).CONCLUSION The method appeared to be accurate, sensitive and reliable,and can be used to control the quality of Xueshuantong injection.
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