The Preparation Of Tougu Xiaotong Capsule And Its Pharmacokinetic Study In Rats

Tougu Xiaotong prescription was Professor of Fujian University of Traditional Chinese Liu Xianxiang’s experience prescription, the capsule Tougu Xiaotong Capsule is one Hospital preparation (Z20100006) of the Second People’s Hospital, it has clinical long used in the treatment of osteoarthritis,and has achieved good results. This research carried out to optimize the extraction and preparation process routes, establish the quality evaluation system, examine the stability,evaluate its pharmacodynamic,study the mechanism, and systematic study the pharmacokinetic behavior characteristics in rats. Intends to develop a innovative traditional Chinese medicine,which effective substance was definitude, mechanism of action was clear, effective and safety with less quantity, quality stable and controllable.By former prescription studied, established the HPLC method of ferulic acid, paeoniflorin, monotropein and isofraxidin of Tougu Xiaotong Capsule for the determination of content,the AUAWC method for studing complex components of traditional Chinese medicine’s pharmacokinetics kinetic characteristics and laws in rats.After determining the prescriptions of Tougu Xiaotong Capsule, to develop a Chinese traditional patent medicine with good effect and less dosage, this study used orthogonal design,analgesic, anti-inflammatory and other tests combined with two evaluation systems-the chemical composition transfer rates and efficacy,carried out preparation process research of Tougu Xiaotong Capsule Extracts including the extraction and purification processes, and laboratory amplified verification test, then through inspected the preparation process.ultimately, determined the preparation route of Tougu Xiaotong Capsule was prepared as follows:Morinda, peony and ligusticum wallichii merger together extracted by alcohol and purified by AB-8resin, sarcandra extracted by water and precipitated by ethanol. obtained Tougu Xiaotong Capsule bulk drug mixed by prescription ratio, after ethanol wet granulation filled in the capsule shells,that got through Tougu Xiaotong Capsules.Conducted efficacy trials and toxicological studies of Tougu Xiaotong Capsules through the hot plate analgesia test in mice,glacial acetic acid-induced writhing response experiments in mice, xylene-induced ear edema experiments in mice and treatment experiments in New Zealand rabbits with knee osteoarthritis.observed the efficacy of Tougu Xiaotong Capsules. As a result, the amount of Tougu Xiaotong Capsule equivalent to double dose of Tougu Xiaotong preparation in clinic could prolong the pain reaction time of the hot plate in mice,significantly inhibited acetic acid-induced writhing in mice, significantly lower xylene-induced mice ear swelling and significantly inhibited the generation of inflammatory cytokines in New Zealand rabbits with KOA.Through acute toxicity in mice and chronic toxicity in rats investigated the toxicity of Tougu Xiaotong Capsules. As a result, the median lethal dose in mice for Tougu Xiaotong Capsule was43.59g/kg equivalent to1002times with the clinical day dose for adult, rat given Tougu Xiaotong Capsules contents0.6g/kg has no significant toxicity,which was safe at those doses.In addition, to investigate the behavior of Tougu Xiaotong Capsules in vivo, this paper conducted the preliminary pharmacokinetic study of Tougu Xiaotong Capsules.Used Area under absorbability-wavelength curve method (referred to as Absorbing Area, AUAWC) to carry out pharmacokinetics of Tougu Xiaotong Capsule contents with oral gavage in rats of different time periods. As a result, the pharmacokinetical compartment model of Tougu Xiaotong Capsule in rats is single-compartment model; the drug had rapid absorption and drug distribution in rats, could reached maximum plasma concentration at about30min;2-fold dose of Tougu Xiaotong Capsule basically eliminated after4h in rats. Therefore, we intend to adopt two-fold dose on clinical applications.Quality control studies of Tougu Xiaotong Capsules. Used thin-layer chromatography method to conduct qualitative identification of morinda officinalis and peony officinalis, As a result, spots are clearly visible with negative non-interference, and easy identification.Used HPLC method to test the levels of paeoniflorin, ferulic acid and the isofraxidin in the prescription, As a result,this product contains ferulic acid15.8mg, paeoniflorin46mg, Isofraxidin204μg each capsule. At the same time.the test method of the determination of multiple assessment methodologies were validated, the results show that the specificity of the method used in the test is strong, simple and accurate. According to the Capsules’General Rule in "Chinese Pharmacopoeia"(2010edition an appendix IL), Content Uniformity, Disintegration Time Limited and Moisture were examined, the results are in line with regulations.The research of stability tests of Tougu Xiaotong Capsules, according to The Bulk Drugs and Pharmaceutical Preparations Stability Test Guidelines in "Chinese Pharmacopoeia"(2010edition two Appendix XIX C), accelerated stability tests and long-term stability test were carried,results show that the trait and level of Tougu Xiaotong Capsules are stable within3months at room temperature (storage conditions) conditions and accelerated conditions.Finally,summarized the progress of the chemical composition, pharmacological effects and quality control for four herbs consisted of Tougu Xiaotong Capsules.