[Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase â ¡b clinical trial].

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Efficacy and safety of Qing-Feng-Gan-Ke Granules in patients with postinfectious cough: study protocol of a novel-design phase III placebo-controlled, double-blind randomized trial.

BACKGROUND: Postinfectious cough (PIC) is a common condition that affects millions of people worldwide every year. There is Western medicine for this condition but the treatment effect is often incomplete. Traditional Chinese medicine (TCM) has been increasingly prescribed for patients with PIC. Preliminary trials on Qing-Feng-Gan-Ke-Granules (QFGKG) conveyed promising results in treating PIC. This protocol describes an ongoing phase III randomized controlled clinical trial, designed according to a novel methodology of "one study, one primary outcome", with the objective of evaluating the efficacy and safety of QFGKG in patients suffering from PIC. METHODS/DESIGN: This is a multicenter, phase III, randomized, double-blind, parallel-group, placebo-controlled clinical trial, comprising two simultaneously conducted study parts, part A and part B, intending to investigate two primary outcomes, i.e. time to cough resolution and cough symptom score, respectively. A total of 480 patients, aged 18 to 65 years, who complain of an ongoing persistent cough that has been lasting ≥ 3 weeks, will be recruited from six participating sites and then randomized to receive QFGKG 12.0 g twice daily or placebo 12.0 g twice daily. Each part will enroll 240 patients, with 180 patients being allocated to the QFGKG group and 60 to the placebo group. DISCUSSION: Although traditional Chinese medicine is a structured intervention that has shown some promise in treating persistent cough, existing unconvincing evidence has noted limitations. This is a rare well-designed and rigorously-controlled, randomized, double-blind trial to evaluate the effects and safety of a Chinese herbal medicine in patients with postinfectious cough, providing tangible benefits for clinical research. Results of this trial are inclined to be conjectured as more truthful by implementing separate study parts that specifically estimate exclusive primary outcome. It will not only provide robust clinical evidence on the efficacy and safety of QFGKG for postinfectious cough, but will also provide a critical piece of information on the availability and superiority of a novel methodology for future clinical trials. The current trial is ongoing with recruitment of the predetermined number of patients being in progress. TRIAL REGISTRATION: The two parts of this trial were separately registered with the Chinese Clinical Trial Registry: ChiCTR-TRC-13003278 (part A); and ChiCTR-TRC-13003337 (part B).

[Treating influenza patients of wind-heat affecting Fei syndrome by jinhua qinggan granule: a double-blinded randomized control trial].

OBJECTIVE: To assess the effect and safety of Jinhua Qinggan Granule (JHG) in treating influenza patients of wind-heat affecting Fei syndrome (WHAFS). METHODS: Totally 136 influenza patients of WHAFS were randomized by stratification into 3 groups, the high dose JHG group (44 cases, 10 g each time), the low dose JHG group (45 cases, 5 g JHG + 5 g placebo each time), and the placebo control group (47 cases, 10 g placebo each time). All medication was administered three times daily for 5 days. The fever disappearance time, the fever disappearance rate, efficacy of TCM syndrome, the disappearance rate of main symptoms and physical signs of flu, the negative rate of virus nucleic acid in the pharyngeal secretion, and safety indicators were assessed. RESULTS: The median fever disappearance time was 32.8 h (95% CI: 22.5-41.0 h) in the high dose JHG group, 26.0 h (95% CI: 14.5-36.5 h) in the low dose JHG group, 39.5 h (95% CI: 29.0-46.0 h) in the placebo control group. There was statistical difference in the median fever disappearance time between the low dose JHG group and the placebo control group (P = 0.011). Three days after treatment, the markedly effective rate of TCM symptoms in the low dose JHG group was 66.7%, higher than that of the placebo control group (38.3%), and its effective rate was superior to that of the high dose JHG group (P = 0.043). Five days after treatment, the recovery rate of the low dose JHG group (42.2%) was higher than that of the high dose JHG group (25.0%, P = 0.026) and that of the placebo control group (14.9%, P = 0.002). The markedly effective rate of the low dose JHG group (86.7%) was higher than that of the placebo control group (55.3%, P = 0.001). Similar effects were obtained in the low dose JHG group and the high dose JHG group, but slightly poor in partial indicators of the high dose JHG group. There was no statistical difference in adverse reaction among these three groups (P > 0.05). CONCLUSIONS: JHG was effective and safe in treating influenza patients of WHAFS. Routinely low dose was the optimal dosage of JHG.

A novel micelle of coumarin derivative monoend-functionalized PEG for anti-tumor drug delivery: in vitro and in vivo study.

In this paper, a novel micelle for anti-tumor drug delivery was reported. Two 7-carboxymethoxy coumarin molecules were immobilized on the terminal group of a methoxy poly(ethylene glycol) chain via l-lysine as linker. The amphiphilic 7-carboxymethoxy coumarin monoend-functionalized methoxy poly(ethylene glycol) (mPEG-Lys-DCOU) chains were self-assembled micelles. Anti-tumor drug doxorubicin was loaded in the mPEG-Lys-DCOU micelles and the release profile was studied. The cytotoxicity of mPEG-Lys-DCOU was evaluated by NIH 3T3 fibroblasts. The drug-loaded micelles were incubated with HepG2 tumor cells to investigate the in vitro anti-tumor effect. The in vivo inhibition efficacy of drug-loaded micelles was carried out on 4T1 breast cancer animal model. The results showed that both hydrophobic and π-π stacking interactions within mPEG-Lys-DCOU amphiphiles were contributed to the self-assembly. Both blank and drug loaded micelles were monodisperse nanoparticles with the average diameters around 300 nm. The release profile exhibited certain pH dependence. The drug release rate at pH = 5.5 was much faster than that at pH = 7.4. mPEG-Lys-DCOU amphiphiles were non-toxic to NIH 3T3 fibroblasts. Both in vitro and in vivo studies demonstrated that the inhibition efficacy of drug-loaded micelles were comparable to that of doxorubicin hydrochloride. mPEG-Lys-DCOU micelles are promising carriers for anti-tumor drug delivery.

Supramolecular self-assembly of monoend-functionalized methoxy poly(ethylene glycol) and α-cyclodextrin: from micelles to hydrogel.

An effective strategy was developed to fabricate a supramolecular hydrogel with the complexation of α-cyclodextrins (α-CDs) and monoend-functionalized low molecular weight methoxy poly(ethylene glycol) (mPEG, Mn=2000) micelles. Hydrophobic cinnamic acid was immobilized on methoxy poly(ethylene glycol) via L-lysine as linker to prepare amphiphilic mPEG. The monoend-functionalized mPEG self-assembled micelles in aqueous solution. The size and size distribution of the micelles were tested by dynamic laser scattering (DLS). The morphology of the micelles was observed by SEM, TEM and AFM. The critical micelle concentration (CMC) was tested and it was 42.5 mg/L. The monodisperse micelles had core-shell structure and the mean diameter was around 40 nanometers. α-cyclodextrins were added in the suspension of micelles to form supramolecular hydrogel with the polypseudorotaxanes complexation. Hydrophilic drug doxorubicin hydrochloride was used as model drug to study the release profile. The results showed that the hydrogel was a promising carrier for drug delivery.

[Andrographolide drop-pill in treatment of acute upper respiratory tract infection with external wind-heat syndrome: a multicenter and randomized controlled trial].

OBJECTIVE: To evaluate the safety and efficacy of andrographolide drop-pill in treatment of acute upper respiratory tract infection with external wind-heat syndrome. METHODS: A multicenter, randomized controlled trial was conducted. In phase I, 202 patients with acute upper respiratory tract infection were randomly divided into two groups: trial group (n=101) and control group (n=101). In phase II, 276 patients with acute upper respiratory tract infection were randomly divided into two groups: trial group (n=138) and control group (n=138). The patients in the trial group received andrographolide drop-pill, at a dose of 1.5 g, three times a day; the patients in the control group received andrographolide tablet, at a dose of 1.5 g, three times a day. The therapeutic courses in both groups were 3 days. Clinical symptoms, physical signs, adverse effects, blood, urine and stool tests, hepatorenal function and electrocardiogram were examined before and after the treatment. RESULTS: After treatment in the phase I, the cure rates in the trial group and the control group were 44.55%, 42.57% (full analysis set, FAS) and 45.00%, 43.00% (per protocol set, PPS), and the total obvious rates were 94.06%, 94.06% (FAS) and 95.00%, 95.00% (PPS), respectively. There were no significant differences between the two groups (P>0.05). In the phase II, the cure rates in the trial group and the control group were 39.13%, 33.82% (FAS) and 38.69%, 33.58% (PPS), and the total obvious rates were 96.38%, 96.32% (FAS) and 96.36%, 96.27% (PPS), respectively. There were no significant differences between the two groups (P>0.05) too. No adverse effects were found in the trial. CONCLUSION: Andrographolide drop-pill is effective and safe in the treatment of acute upper respiratory tract infection with external wind-heat syndrome.