| Objective: To develop a new formula: stomach and colon two-step, colon-targeted sustained release pellet. Chang' an Kang, the clinical effective decoction in treating ulcerative colitis (UC) was reformulated into pellets according to TCM theory. It was designed according to its "excess in branch, deficient at root" characteristics, the root-targeting drugs such as Astragalus are released in the stomach and absorbed into blood to have general effects; whereas other drugs such as Coptis are targeted to colon to have localized effects through coating method. In other words, this formula is a stomach and colon two-step, colon-targeted sustained release pellet.Preliminary feasibility discussion of this TCM composite formula were conducted through effectiveness preliminary test and clinical test, in vitro release, in vivo biological release, and the foundation for further formula redesign were laid. Hope to develop new method and new formula in treating UC.Methods: (1) Preliminary pharmacological research: the preliminary effectiveness experiments were performed through the analgesia and anti-inflammatory test on mouse model and acetic acid rat mode; also the effect of different administration methods through acetic acid rat model to collect experimental data for formula design; (2) Process technology: optimum extraction factors were determined by crossing designs and comparative experiments, the production procedure for filling and coating material of stomach-released and colon-targeted pellets was selected through rolling into ball methods and streamline bed coating technology; the best procedure for 2 kinds of coating material Eudragit and Surelease were also determined; (3)//? vivo test of human subjects: in vivo clinical test were conducted on healthy volunteers and two kinds of colon-targeted pellets were evaluated and compared through BaSO X-ray photography; (4) Pharmacological research: pharmacological investigation was conducted with UC rabbit model; (5) Quality specification of the pellets: the content of Astragalin IV was determined through Thin Layer Chromatography scanning(TLS), Berberine was through HPLC, other drugs were evaluated by TLC methods.Results: (l)Preliminary pharmacological investigation shown: Chang' an kang has significant inhibitory effect to colon mucus lesions of UC acetic acid rat model, it also have the anti-inflammatory and analgesia effects. Different delivery methods, and treatment of UC with general and specific treatment combined together can achieve better therapeutic results; (2) Through procedure selection, the best processing method was determined as follows: the best result is achieved by: decocting Astragali, Psoralae, Aucklandiae with water and making all the extractions into powder, mixing drug powder and starch at 6:1 percentage, rolling into pellets, increasing weight about 3% with Opadry coating; theeffective component Berberrine of Coptis was used; citric acid extraction of Lonicerae was used; raw Sanguisorbae was extracted with 70% ethanol; drug powder and CMS-Na were mixed at 6:1 percentage, rolling into sustained release pellets, in vitro release experiments shown a total release in 5h; two coating material, Eudragit L100 and Eudragit S100 (1 ?1.5 ) with coating weight of 22.2% and including the 10% weight of Surelease with 10% HPMC, all achieved colon-targeted drug release; (3) In vivo test of human subjects: the two kinds of pellets with different coating materials all pass safely through stomach and small intestine, begin release after reaching colon. Chang' ankang pellets coating with Eudragit by combining pH-dependent and time-dependent together have better results; (4) Pharmacological research: Chang' ankang was shown to have good inhibition effect to the colon mucus lesion of UC rabbit model, it also can reduce the edama of colon, the best dose is moderate. It shown better therapeutic results compare to Chang' ankang without coating; (5) Quality control research: The experimental methods are controllable and reproducible as the content of Astr...
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