Modern and international studies on new traditional Chinese medicines are the main trend of the development of traditional Chinese medicines at present. In Australia, new traditional Chinese medicines refer to complementary medicines, which are mainly registered and launched as listed medicines. The application documents of registered (listed) medicines in Australia mainly cover detailed description of active pharmaceutical ingredients, pharmacological and toxicological studies, dosage form and adverse effects. Each part has detailed specifications and instructions, which helps ensure that applicants could accurately understand the requirements in application for registering (listing) medicines, and provides very important reference to the studies and development of new traditional Chinese medicines in China.
Australia ; Drug Approval ; Drug Evaluation ; Medicine, Chinese Traditional

The new drug of Chinese herbal prescription, which is the best carrier for the syndrome differentiation and treatment of Chinese medicine and is the main form of the new drug research and development, plays a very important role in the new drug research and development. Although there are many sources of the prescriptions, whether it can become a new drug, the necessity, rationality and science of the prescriptions are the key to develop the new drug. In this article, aiming at the key issues in prescriptions design, the source, classification, composition design of new drug of Chinese herbal prescriptions are discussed, and provide a useful reference for research and development of new drugs.
Drug Design ; Drug Prescriptions ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans

OBJECTIVETo discuss that pathogenesis evolvement regularity of Chinese miniature swine with phlege-stasis cementation syndrome of coronary heart disease.

METHODEighteen Chinese miniature swine were randomly divided to the normal control group, the model group and the Danlou tablet group, with six swine in each group. Except for the normal control group, all of the other groups were fed with high fat diet for two weeks. The coronary heart disease model with phlegm-stasis cementation syndrome was established by injuring left anterior descending artery with interventional balloons and continuously feeding with high fat diet for eight weeks. The levels of BMI, hemorheological parameters, lipids in serum and inflammatory cytokines were observed at the 0th (before the experiment), 2nd (before operation or drug administration), 6th (four weeks after drug administration) and 10th week (eight weeks after drug administration) of study. The levels of TG and TC in liver and the pathological changes in coronary artery tissues were also observed at the end of study.

RESULTCompared with the normal control group, the model group had showed significant increase in the levels of TC, TG, LDL-C and VLDL-C in serum (P < 0.01) from the second week to the end of the experiment, with notable rise in the whole blood viscosity under the shear rates of 5 s(-1) and 60 s(-1). At the 6th week, the levels of BMI and TG and TNF-alpha in serum significantly increased. At the 10th week, the levels of BMI and hs-CRP, IL-6 and TNF-alpha in serum significantly increased as well, with remarkable increase in coronary stenosis, intimal thickness and the ratio between intimal thickness and media thickness (P < 0.05 and P < 0.01), and significant rise in TC and TG in livers (P < 0.01). Compared with the model group, the Danlou tablet group showed obvious reduction in severity of coronary artery lesion, intimal thickness and lumen stenosis ratio and ratio between intimal thickness and media thickness (P < 0.01), BMI, TC, TG, LDL-C and VLDL-C in serum, TC and TG in liver, as well as hs-CRP, IL-6 and TNF-alpha levels in serum (P < 0.05 and P < 0.01), with notable decline in the whole blood viscosity under the shear rates of 5 s(-1) and 60 s(-1).

CONCLUSIONThe interaction of phlegm, blood stasis and toxin syndromes helps promote the progress and development of AS plaques, which is the key pathogenesis of phlegm-stasis cementation syndrome in coronary heart disease.

Animals ; Body Weight ; Coronary Disease ; blood ; physiopathology ; Female ; Hemodynamics ; Inflammation Mediators ; metabolism ; Lipids ; blood ; Liver ; metabolism ; Male ; Medicine, Chinese Traditional ; Swine ; Swine, Miniature

OBJECTIVETo establish the "clinical-mimetic" Chinese medicine symptom complex score method for the coronary heart disease Chinese miniature swine model with phlegm-stasis cementation syndrome, in order to observe the effect of formula of removing both phlegm and blood stasis (TYTZ) on the Chinese medicine symptom complex score for the coronary heart disease Chinese miniature swine model with phlegm-stasis cementation syndrome.

METHODTotally 36 Chinese miniature swine were randomly divided to the normal control group, the model group, the Shujiangzhi group, and TYTZ groups with doses of 2.0, 1.0 and 0.5 g x kg(-1), with six in each group. Except for the normal control group, all of the other groups were fed with high fat diet for two weeks. The coronary heart disease model with phlegm-stasis cementation syndrome was established by injuring left anterior descending artery with interventional balloons and continuously feeding with high fat diet for eight weeks. After the operation, the groups were administered with drugs for eight weeks. Their main symptoms, accompanied symptoms, tongue and pulse signs of the coronary heart disease Chinese miniature swine with phlengm-stasis cementation syndrome were observed according to the symptom-graded scoring method.

RESULTCompared with the model group, TYTZ in different doses could reduce the scores of main symptoms at the 6th and 10th week. Specifically, TYTZ in low dose could reduce the scores of tongue at the 6th week and the scores of accompanied symptoms, and tongue and pulse signs at the 10th week; And TYTZ in high dose could decrease all symptom scores at the 6th and 10th week (P < 0.05 or P < 0.01).

CONCLUSIONTYTZ can improve the scores of the main symptoms, accompanied symptoms, tongue and pulse signs in coronary heart disease Chinese miniature swine with phlegm-stasis cementation syndrome. It is suggested that the "clinical-mimetic" objective scoring for syndromes of Chinese miniature swine is of great significant to the development of new traditional Chinese medicine drugs.

Animals ; Chemistry, Pharmaceutical ; Coronary Disease ; blood ; diagnosis ; physiopathology ; therapy ; Female ; Male ; Medicine, Chinese Traditional ; methods ; Swine ; Swine, Miniature

OBJECTIVETo comparatively analyse the objective characteristics of different syndrome types of qi-disturbance-induced blood stasis syndrome (QDBS) in the pathogenetic evolution of unstable angina coronary heart disease (UA-CHD).

METHODSSeventy-eight patients with UA-CHD of QDBS were differentiated into 2 groups: 55 in the qi-deficiency-induced blood-stasis syndrome group (A) and 23 in the qi-stagnation-induced blood-stasis syndrome group (B). The comparative analysis on them was carried out through comparing their blood pressure, glucose and lipid metabolisms, coagulation function, thyroid function and inflammation reaction changes, etc.

RESULTSIn the pathogenetic process of qi-disturbance induced blood stasis, the initiating age, levels of HbA1c, TSH, PT and APTT between the two groups were significantly different (P < 0.05). Levels of TNF-alpha and LN were higher and levels of sIgA lower in patients than those in healthy subjects (P < 0.05).

CONCLUSIONSInflammation immune reaction may play an important role in the pathogenetic process of blood-stasis syndrome, and the functional disturbance of hypothalamus, pituitary and endocrinal secretion induced by emotional stress is possibly the essence of qi-stagnation induced blood stasis syndrome.

Adult ; Angina, Unstable ; diagnosis ; Coronary Disease ; Diagnosis, Differential ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Qi

OBJECTIVETo establish a disease-syndrome conjugated animal model, the mini-swine coronary heart disease (CHD) model of phlegm-stasis cementation syndrome type, by high fat diet feeding and coronary artery balloon injury.

METHODSMini-swine were randomly divided into the control group and the model group, 6 in each group. They were fed with common forage and high fat forage respectively for 10 weeks and the coronary left anterior descending branch in the model group was injured by balloon intervention technique after 2-week feeding to establish CHD model. The model establishment and its physiopathological indices were evaluated by examinations on body mass index (BMI), blood levels of lipid, high-sensitivity C-reactive protein (hs-CRP), body surface electrocardiograph (BS-ECG), coronary angiography and pathological indices.

RESULTSBMI, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), hs-CRP, sigma-ST and N-ST indicated by BS-ECG in the model group were all higher than those in the control group respectively (P < 0.05 or P < 0.01). Coronary angiography showed coronary lumen narrowed with apparent lumen loss, showing a significant difference as compared with the control group (P < 0.01). In EVG staining, the diameters of lumen in the model group was obviously narrow with intima proliferation, also significantly different to those in the control group (P < 0.01).

CONCLUSIONDisease-syndrome combined model for coronary heart disease of phlegm-stasis cementation syndrome type in mini-swine could be established by high fat diet feeding with coronary arterial injury.

Animals ; Coronary Disease ; etiology ; Diagnosis, Differential ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Female ; Male ; Medicine, Chinese Traditional ; methods ; Random Allocation ; Swine ; Swine, Miniature ; Syndrome

OBJECTIVETo observe the effect of formula of removing both phlegm and blood stasis (TYTZ) in inhibiting the inflammatory reaction in Chinese mini-swine with coronary atherosclerosis.

METHODTotally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Shujiangzhi group and TYTZ groups with does of 2.0, 1.0 and 0.5 g x kg(-1), and six each in every group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary atherosclerosis model. In the 8th week after the operation and administration, the intravascular ultrasound was adopted to observe the coronary artery plaque burden of each group and the pathological morphology of coronary artery. Such inflammatory factors as high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were detected by ELISA. The expression of NF-kappaB p65 nuclear translocation was observed by the immunohistochemical method.

RESULTCompared with the normal control group, the model group showed significant increase in the coronary artery plaque burden at the end of the experiment (P < 0.01), notably abnormal structural changes in atherosclerotic vascular tissues, luminal stenosis, a large number of foam cells and inflammatory cell infiltration, remarkable growth of hs-CRP, TNF-alpha and IL-6 levels (P < 0.01). The immunohistochemical staining also showed the significant increase in the NF-kappaB p65 nuclear translocation of coronary artery of Chinese mini-swine in the model group. Compared with the model group, TYTZ could significantly attenuate atherosclerotic plaque burden (P < 0.01), inhibit the coronary luminal stenosis, reduce inflammatory cell infiltration, decrease such inflammatory cell factors as hs-CRP, TNF-alpha and IL-6 in serum, and inhibit the NF-kappaB p65 nuclear translocation of coronary artery (P < 0.05 or P < 0.01).

CONCLUSIONTYTZ can reduce the downstream inflammatory reaction by controlling NF-kappaB p65 nuclear translocation, so as to inhibit the occurrence and development of coronary atherosclerotic plaque in Chinese mini-swine.

Animals ; C-Reactive Protein ; metabolism ; Coronary Artery Disease ; blood ; complications ; drug therapy ; pathology ; Female ; Inflammation ; complications ; Interleukin-6 ; blood ; Male ; Medicine, Chinese Traditional ; methods ; Mucous Membrane ; drug effects ; secretion ; Swine ; Swine, Miniature ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo evaluate that the effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome.

METHODTotally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. After the operation, they were administered with drugs for 8 weeks. The changes in the myocardial ischemia were observed. The changes in the cardiac function and structure were detected by cardiac ultrasound and noninvasive hemodynamic method.

RESULTCompared with the normal control group, the model group showed significant increase in myocardial ischemia and SVR and obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05 or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs, EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac function, and improve the abnormal cardiac structure and function induced by ischemia (P <0. 05 or P <0. 01).

CONCLUSIONTYTZ shows a significant effect in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. The clinical cardiac function detection method could be adopted to correctly evaluate the changes in the post-myocardial ischemia cardiac function, and narrow the gap between clinical application and basic experimental studies.

Animals ; Coronary Circulation ; Coronary Disease ; diagnostic imaging ; metabolism ; physiopathology ; therapy ; Heart ; physiopathology ; Hemodynamics ; Medicine, Chinese Traditional ; methods ; Mucus ; metabolism ; Swine ; Swine, Miniature ; Ultrasonography

OBJECTIVETo observe effect of formula of removing both phlegm and blood stasis (TYTZ) in improving hemorheology and blood fat of mini-swine with coronary heart disease of phlegm-stasis cementation syndrome.

METHODThirty-six Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Shujiangzhi group and TYTZ groups with doses of 2.0, 1.0 and 0.5 g x kg(-1), with six mice in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. In the 8th week after the operation and administration, the changes in hemorheological parameters, serum lipid level, myocardial ischemia level and range were observed.

RESULTCompared with the normal control group, the model group showed significant increase in serum TC, TG, LDL-C and VLDL-C levels (P < 0.01), whole blood viscosity under the shear rate of 5 s (-1) and 60 s (-1) (P < 0.01), and myocardial ischemia degree and range (P < 0.01). Compared with the model group, TYTZ groups revealed significant decrease in myocardial ischemia degree and range (P < 0.01), serum TC, TG, LDL-C and VLDL-C levels (P < 0.05 or P < 0.01) and whole blood viscosity under the shear rate of 5 s(-1) and 60 s(-1) (P < 0.05).

CONCLUSIONTYTZ could improve the abnormal hemorheology in Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome, and regulate serum lipid, with a certain efficacy for coronary heart disease of phlegm-stasis cementation syndrome.

Animals ; Coronary Disease ; blood ; metabolism ; physiopathology ; therapy ; Female ; Hemorheology ; Lipids ; blood ; Male ; Medicine, Chinese Traditional ; methods ; Mucous Membrane ; secretion ; Swine ; Swine, Miniature

OBJECTIVETo study the protective effect of formula of removing both phlegm and blood stasis (TYTZ) on myocardial tissues of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome.

METHODTotally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and TYTZ groups with doses of 2.0, 1.0, 0.5 g x kg(-1), with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome in Chinese mini-swine. After the operation, they were administered with drugs for 8 weeks. The SOD activity and MDA content of each group were observed at the 0th week (before the experiment), the 2nd week after the high-fat diet (before the operation or drug administration) , the 6th week after the high-fat diet (4 weeks after the drug administration) and the 10th week after the high-fat diet (8 weeks after the drug administration). Meanwhile, the myocardial enzymogram test and the HE staining pathological observation were performed at the end of the experiment. The changes in the myocardial cell ultra-structure were observed under transmission electron microscope.

RESULTCompared with the normal control group, the model group showed significant decrease in serum SOD activity and notable increase in MDA content from the 2nd week to the end of experiment (P < 0.05 and P < 0.01). In the 10th week, the CK, LDH and CK-MB levels in serum also significantly increased in the model group (P < 0.05 and P < 0.01), with obvious structural abnormality in myocardial tissue pathologic morphology and ultra-structure. Compared with the model group, TYTZ groups showed specific increase in serum SOD activity and oblivious decrease in the MDA level (P < 0.05 or P < 0.01). Meanwhile, TYTZ could significantly decrease serum CK and LDH levels in the model group (P < 0.05 or P < 0.01), attenuate the ischemia injury of myocardial tissue, and improve the ultra-structure of cardiomyocytes.

CONCLUSIONTYTZ shows an obvious protective effect on the myocardial injury in Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. Its mechanism is related to the resistance against free radical oxidation injury and the inhibition of the lipid per-oxidation.

Animals ; Coronary Artery Disease ; genetics ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Mucus ; drug effects ; metabolism ; Myocardium ; metabolism ; Protective Agents ; administration & dosage ; Swine ; Swine, Miniature