Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Correlation analysis of plasma N-terminal pro-brain natriuretic peptide, p-selectin and type 2 diabetes mellitus complicated with acute coronary syndrome / 解放军医学杂志

[Abstract] Objective To investigate the relationship between plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), P-selectin (PS) and type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS). Methods Two hundred and twenty-eight patients with chest pain, admitted in the Department of Cardiology of Langfang Traditional Chinese Medicine Hospital and the Affiliated Hospital of North China University of Science and Technology from July 2017 to April 2018, were selected in present study, including 32 patients with T2DM, 124 patients with ACS, and 72 patients with T2DM complicated with ACS (DA group). ELISA was performed to detect the levels of plasma NT-pro-BNP and PS, and venous blood was taken on an empty stomach to complete a general biochemical project. Based on the results of coronary angiography performed by using Judkins method, the Gensini score was used to evaluate the degree of coronary stenosis. The general clinical data of the 3 groups were compared, and logistic regression was performed to analyze the risk factors for ACS in patients with T2DM. Results No statistical difference existed in gender, history of hypertension, smoking, body mass index, age, and creatinine among the three groups; The levels of low-density lipoprotein cholesterol and triglyceride were higher in DA group [(3.16±0.98)mmol/L and (2.21±1.36)mmol/L] than in T2DM and ACS group [(2.83±0.91)mmol/L, (1.65±1.05)mmol/L and (2.84±0.92)mmol/L, (1.68±0.97)mmol/L] with significant difference (P<0.05). The left ventricular ejection fraction was lower in DA group (58.97±7.35)% than in T2DM and ACS groups [(63.48±7.37)% and (61.26±7.68)%, respectively] with statistically significant difference (P<0.01). The PS was higher in DA group (48.30±13.61)ng/L than in ACS group (38.87±9.12)ng/L, and in ACS group than in T2DM group (21.46±12.30)ng/L; The C-reactive protein was higher in DA group [(27.63±11.87)mg/L] than in ACS group (20.21±9.32)mg/L, and in ACS group than in T2DM group [(10.30±4.22)mg/L]; The NT-pro-BNP M(Q1, Q3) was higher in DA group [419(154, 1350)pg/ml] than in ACS group [120(43, 416)pg/ml], and in ACS group than in T2DM group [22(12, 54)pg/ml]; The Gensini scores was higher in DA group (138.39±88.31) than in ACS group (82.12±63.08), and in ACS group than in T2DM group (39.98±32.12), all the differences listed above were statistically significant (P<0.01). It had been confirmed by multivariate logistic regression analysis that the levels of PS and high-sensitivity C-reactive protein were the risk factors for ACS in patients with DM, their OR estimates were 1.138 (95%CI 1.089-1.990, P<0.01) and 1.656 (95%CI 1.189~2.307, P<0.01), respectively. Conclusion High levels of PS and high-sensitivity C-reactive protein are the independent risk factors for ACS in patients with T2DM. NT-pro-BNP was not associated with ACS in patients with T2DM.

Chemical constituents from flowers of Wikstroemia chamaedaphne and their anti-hepatitis B virus activity / 中草药

Objective: To study the anti-hepatitis B virus diterpenoids from flowers of Wikstroemia chamaedaphne. Methods: The chemical constituents of the plant were isolated and purified by column chromatography and their structures were elucidated on the basis of physicochemical properties, X-ray, and spectral data. The antivirus assay was tested by MTT and ELISA methods. Results: Six daphnane-type diterpenoids and one tigliane-type diterpenoid were obtained and determined as simplexin (1), pimelotide A (2), pimelotide C (3), wikstroelide E (4), pimelea factor S6 (5), pimelea factor S7 (6), and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate (7), along with two flavonoid glycosides luteolin-4'-O-β-D-glucoside (8) and isoquercitrin (9). Compounds 1-4 and 7 showed certain cytotoxicity on HepG2.2.15 and compound 3 exhibited strong anti-hepatitis B virus activities with IC50 value of 0.016 μg/mL against HBV surface antigen (HBsAg), with TI (Therapeutic Index) value of 355.63. Conclusion: Compounds 7 and 8 are isolated from the genus for the first time. And it is the first time to report the X-ray structure of compound 2 and the anti-hepatitis B virus activity of compound 3 (pimelotide C).

Online endpoint detection algorithm for blending process of Chinese materia medica / 中国中药杂志

Blending process, which is an essential part of the pharmaceutical preparation, has a direct influence on the homogeneity and stability of solid dosage forms. With the official release of Guidance for Industry PAT, online process analysis techniques have been more and more reported in the applications in blending process, but the research on endpoint detection algorithm is still in the initial stage. By progressively increasing the window size of moving block standard deviation (MBSD), a novel endpoint detection algorithm was proposed to extend the plain MBSD from off-line scenario to online scenario and used to determine the endpoint in the blending process of Chinese medicine dispensing granules. By online learning of window size tuning, the status changes of the materials in blending process were reflected in the calculation of standard deviation in a real-time manner. The proposed method was separately tested in the blending processes of dextrin and three other extracts of traditional Chinese medicine. All of the results have shown that as compared with traditional MBSD method, the window size changes according to the proposed MBSD method (progressively increasing the window size) could more clearly reflect the status changes of the materials in blending process, so it is suitable for online application.

Effects of Shenqi preparation on anti-fatigue and anti-oxidant functions in mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore effects of Shenqi preparation,Traditional Chinese Medicine, on anti-fatigue and anti-oxidant functions.</p><p><b>METHODS</b>One hundred and twenty mice were randomly divided into control group and 3 experimental groups. The high, medium and low-dose of Shenqi preparation were given to the 3 experimental groups respectively, while distilled water to the control group for 15 d. The loaded swimming time, the level of lactate, serum urea nitrogen (SUN), muscle and liver glycogen, liver super-oxide dismutase (SOD), the content of malondialdehyde (MDA), glutathione peroxidase(GSH-Px) were assayed.</p><p><b>RESULTS</b>The loaded swimming test showed that the exhausted swimming time of 3 experimental groups [(296.0 +/- 25.3)s, (437.0 ĝ 38.9)s, (595.0 +/- 53.9)s respectively] was longer than that of control group [(231.0 +/- 22.5)s, P < 0.05, P < 0.01]. The liver glycogen content of the high and medium-dose experimental groups were higher than that of control group respectively (P < 0.01). The SUN content of each experimental group was less than that of the control group (P < 0.01, P < 0.05). Moreover,in the medium and high dose experimental groups, less accumulation of lactate was found (P < 0.01, P < 0.05), and the content of liver SOD and GSH-Px was higher (P < 0.01, P < 0.05). The content of liver MDA in high-dose experimental group was less than that of the control group (P < 0.05).</p><p><b>CONCLUSION</b>Shenqi preparation, especially the high and medium-dose experimental groups, is able to improve exercise tolerance and has anti-fatigue and anti-oxidant effects in mice.</p>

DS147 improves pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation / 华中科技大学学报（医学）（英德文版）

The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.

Controlled clinical trials on the effects of Chinese traditional medicine for the treatment of osteoarthritis of knee joint at early stage and its MRI changes / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the effects of Chinese traditional medicine for the treatment of osteoarthritis of knee joint at early stage, as well as to observe the changes of articular cartilage in MRI before and after the treatment.</p><p><b>METHODS</b>Sixty patients were divided into two groups according to Doll's law, 32 patients in the treatment group (6 male and 26 female, with an average age of 52.2 years, ranging from 43 to 65 years, 40 joints), 28 patients in the control group (5 male and 23 female, with an average age of 54.4 years, ranging from 42 to 65 years, 33 joints). The patients in the test group were given Chinese traditional medicine orally, and patients in the control group were given celecoxib and the glucosamine hydrochloride orally for three months. MR scan and ISOA score were given respectively before and after treatment. After the treatment, the articular cartilage changes of the weight bearing area were observed to evaluate the therapeutic effects.</p><p><b>RESULTS</b>All the patients were followed up ranging from 13 to 17 months, with an average of 15.3 months. According to MRI evaluation, 15 joints got an excellent result, and 17 joints got a good result in the treatment group, the total excellent and good rate was 80.0%; and in the control group, above data were 8, 11 and 57.6% respectively. The average ISOA score of the treatment group after treatment was 0.35 +/- 0.16, and in the control group was 3.68 +/- 0.18. There was significant differences between the two groups of ISOA score (t = 6.94, P<0.05).</p><p><b>CONCLUSION</b>Chinese traditional medicine can significantly alleviate or inhibit the cartilage degeneration of knee osteoarthritis at early stage and improve joint function. It had significant clinical effects.</p>

Advances of studies on acupuncture and moxibustion for treatment of spastic paralysis after stroke / 中国针灸

<p><b>OBJECTIVE</b>To introduce progresses of studies on acupuncture and moxibustion for treatment of spastic paralysis after stroke.</p><p><b>METHODS</b>The literature about acupuncture and moxibustion for treatment of spastic paralysis after stroke in recent ten years were reviewed from the clinical and mechanism studies and so on.</p><p><b>CONCLUSION</b>A great number of clinical and mechanism studies have proved that acupuncture and moxibustion therapy can relieve spastic paralysis after stroke, with better therapeutic effect, no side-effects, flexible selection of acupoints and more methods, but clinical and mechanism studies still need further to be improved and raised.</p>