ABSTRACT
A content determination method based on ~1H-qNMR was developed for the determination of total ginsenosides in Shenmai Injection. The parameters were optimized with CD_3OD as the solvent, dimethyl terephthalate as the internal standard, the peak at δ 8.11 as the internal standard peak, and the peaks at δ 1.68 and δ 0.79 as quantitative peaks of total ginsenosides. The developed ~1H-qNMR-based method was validated methodologically. The results showed that the method could achieve accurate measurement of total ginsenosides in Shenmai Injection in the range of 0.167 6-3.091 1 mmol·L~(-1). The developed ~1H-qNMR-based method for total ginsenosides is simple in operation, short in analysis time, strong in specificity, independent of accompanying standard curve, and small in sample volume, which can serve as a reliable mean for the quality control of Shenmai Injection. This study is expected to provide new ideas for the development of quantification methods of total ginsenosides.
Subject(s)
Drug Combinations , Drugs, Chinese Herbal , Ginsenosides/analysis , Quality ControlABSTRACT
Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.
Subject(s)
Chromatography, High Pressure Liquid , Drug Combinations , Drugs, Chinese Herbal/chemistry , Proton Magnetic Resonance Spectroscopy , Rhizome/chemistryABSTRACT
The present study established a quality evaluation method for ginsenoside reference substances based on quantitative nuclear magnetic resonance(qNMR) spectroscopy. ~1H-NMR spectra were collected on Bruker Avance Ⅲ 500 MHz NMR spectrometer equipped with a 5 mm BBO probe. The acquire parameters were set up as follows: pulse sequence of 30°, D_1=20 s, probe temperature= 303 K, and the scan number = 32. Dimethyl terephthalate, a high-quality ~1H-qNMR standard, was used as the internal standard and measured by the absolute quantitative method. Methyl peaks of comparatively good sensitivity were selected for quantification, and linear fitting deconvolution was adopted to improve the accuracy of integration results. The qNMR spectroscopy-based method was established and validated, which was then used for the quality evaluation of ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, ginsenoside Rd, and notoginsenoside R_1. The results suggested that the content of these ginsenoside reference standards obtained from the qNMR spectroscopy-based method was lower than that detected by the normalization method in HPLC provided by the manufacturers. In conclusion, the qNMR spectroscopy-based method can ensure the quality of ginsenoside reference substances and provide powerful support for the accurate quality evaluation of Chinese medicine and its preparations. The qNMR spectroscopy-based method is simple, rapid, and accurate, which can be developed for the quantitative assay of Chinese medicine standard references.
Subject(s)
Chromatography, High Pressure Liquid/methods , Ginsenosides/analysis , Magnetic Resonance Spectroscopy/methods , Proton Magnetic Resonance Spectroscopy , Reference StandardsABSTRACT
Chinese medicinal injection, made of active components extracted from Chinese medicine or Chinese medicinal compound, is a novel dosage form of Chinese patent medicine in China and is pivotal in the traditional Chinese medicine(TCM) industry. The quality control standard of Chinese medicinal injection determines its safety and efficacy. The quantitative nuclear magnetic resonance(qNMR) spectroscopy is a non-targeted, non-invasive, and non-destructive technique with high reproducibility, short measurement time, convenient sample preparation, a broad range of linearity, and no requirement on the reference substance of tested components, which is advantageous as compared with traditional chromatographic methods, and it can provide information about the molecular composition of the tested samples. Therefore, in light of multiple challenges in the quality control of Chinese medicinal injection, such as complex composition, difficulties in quantitative analysis, and the shortage of reference substances, the application of qNMR spectroscopy combined with chemometrics techniques was proposed for the quality evaluation of Chinese medicine reference substances, Chinese medicinal injection, and intermediates in the production process, as well as for the stability analysis of Chinese medicinal injection. This study is expected to provide references for the application of qNMR spectroscopy in the quality control of Chinese medicinal injection.
Subject(s)
Magnetic Resonance Spectroscopy , Medicine, Chinese Traditional , Quality Control , Reproducibility of ResultsABSTRACT
Most of the neuromuscular diseases are rare diseases, and Duchenne muscular dystrophy and Spinal muscular atrophy are common types of neuromuscular diseases. An important feature of neuromyopathy is progressive disability. Therefore, functional assessment is very important to evaluate the severity, motor function and activities of patients with neuromuscular disease. At present, the functional assessment invoved muscle strength, range of motion, posture and activities, and applied various functional assessment tools. However, there is no unified standard yet. Accurate and reasonable evaluation is essential for multidisciplinary management team to develop individualized treatment plan for patients.
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Objective: To optimize the lime milk-sulfuric acid process of Salviae Miltiorrhizae Radix et Rhizoma (SMRR) aqueous concentrate in the pretreatment of the manufacture of Danshen Chuanxiongqin Injection (DCI) based on the quality by design (QbD) concept. Methods Fishbone diagram method was applied to conduct preliminary risk assessment of various process parameters in lime milk-sulfuric acid process of SMRR aqueous extracts. Nine potential critical process parameters (CPP), including mass fraction of lime milk, flow rate of the lime milk addition, stirring speed, stirring time after lime milk addition, mass fraction of sulfuric acid, flow rate of the acid addition, stirring time after acid addition, standing time, and standing temperature, were identified. Plackett-Burman (PB) experiment design method was used to further screen the nine potential CPPs. As the result, the mass fraction of lime milk, stirring time after lime milk addition, stirring time after acid addition, and the standing time were filtered as CPPs of the lime milk-sulfuric acid process. A partial least squares regression models of critical process parameters and critical quality attributes were established using the central composite design and the design space methodology. Results: The recommended operation space of the lime milk-sulfuric acid process in the pretreatment of the manufacture of DCI was as follow: mass fraction of lime milk of 12.0%-13.0%, stirring time after lime milk addition of 40-50 min, stirring time after acid addition of 30-35 min, and standing time of 16-20 h. Conclusion: Operation in the design space is helpful to improve the consistency of lime milk-sulfuric acid process. This study is of valuable reference to actual industrial production.
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Coronary artery disease (CAD) is a multifactorial disease in which inflammation plays a central role.This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio (NLR),the Global Registry of Acute Coronary Events (GRACE) score with in-hospital mortality of elderly patients with acute myocardial infarction (AMI) in an attempt to explore the prognostic value of these indices for elderly AMI patients.One thousand consecutive CAD patients were divided into two groups based on age 60.The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records.The NLR and GRACE score were calculated.In the elderly (≥60 years),patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) had significantly higher NLR than did those with unstable angina (UA) and stable angina pectoris (SAP) (P＜0.01).The NLR was considerably elevated in older AMI patients compared with their younger counterparts (＜60 years) (P＜0.05).In elderly AMI patients,the NLR was considerably higher in the high-risk group than in both the low-risk and medium-risk groups based on the GRACE score (P＜0.05 and P＜0.01,respectively),and the NLR was positively correlated with the GRACE score (r=0.322,P＜0.001).Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group (P＜0.05).By curve receiver operator characteristic curve (ROC) analysis,the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve (AUC) 0.771 and 0.787,respectively,P＜0.001].It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.
ABSTRACT
Coronary artery disease (CAD) is a multifactorial disease in which inflammation plays a central role.This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio (NLR),the Global Registry of Acute Coronary Events (GRACE) score with in-hospital mortality of elderly patients with acute myocardial infarction (AMI) in an attempt to explore the prognostic value of these indices for elderly AMI patients.One thousand consecutive CAD patients were divided into two groups based on age 60.The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records.The NLR and GRACE score were calculated.In the elderly (≥60 years),patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) had significantly higher NLR than did those with unstable angina (UA) and stable angina pectoris (SAP) (P＜0.01).The NLR was considerably elevated in older AMI patients compared with their younger counterparts (＜60 years) (P＜0.05).In elderly AMI patients,the NLR was considerably higher in the high-risk group than in both the low-risk and medium-risk groups based on the GRACE score (P＜0.05 and P＜0.01,respectively),and the NLR was positively correlated with the GRACE score (r=0.322,P＜0.001).Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group (P＜0.05).By curve receiver operator characteristic curve (ROC) analysis,the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve (AUC) 0.771 and 0.787,respectively,P＜0.001].It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.
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[Objective]To investigate efficacy and toxicity of a new modified FOLFIRINOX regimen(mFOLFIRI-NOX)as first-line chemotherapy for the patients with metastatic pancreatic adenocarcinoma(MPC).[Methods]20 patients with metastatic pancreatic adenocarcinoma(MPC)accepted mFOLFIRINOX arm(oxaliplatin 60 mg/m2,irinotecan 150 mg/m2,bolus of 5-FU 400 mg/m2,continuous infusion of 5-FU 2 400 mg/m2)first-line treatment and evaluated the curative effect and side effect after 3 cycles by imaging and laboratory at Sun Yat-sen Memorial Hospital from December 2012 to December 2016.The primary endpoint was overall survival(OS).The second endpoint was response rate(ORR) and toxicity.[Results]Four patients were excluded according to exclusion criteria. A total of 16 patients were enrolled including 7 males and 9 females.The median age is 55 years(ranging from 43 to 67 years).The median cycle of chemo-therapy was 4.5(3-15). The ORR was 31.3% including 5 patients with partial response,9 patients with stable disease and 2 patients with progression disease.The median follow-up duration was 14.1(2.7-24.5)months.The median OS was 16.6 months(95%CI,11.36-21.84). Overall survival rates at 6,12months were 80%and 55.6%,respectively. Three patients were presented grade 3-4 adverse events.[Conclusion]The new mFOLFIRINOX regimen improved survival of patients with MPC with tolerated toxicity as first line treatment.
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The skin mycoses, perticularly dermatophytoses, in Lanzhou district, Northwestern China, was investigated during July 2002-June 2003. The specimens from patients suspected of having dermatomycoses were examined microscopically in KOH preparations and cultured on Sabouraud dextrose agar (SDA). Among 1443 suspected cases, 594 were KOH positive and 221 cultures of fungi were isolated. The most frequently isolated fungi were Trichophyton rubrum (43.9%) Trichophyton mentagrophytes (29.4%) and Candida species (14.0%). The frequency of tinea pedis, onychomycosis and tinea manuum were 38.7, 27.8 and 13.5%, respectively. In Lanzhou district, tinea pedis is the most commonly seen dermatophytoses, and T. rubrum is the most frequent etiologic agent.
