| Objective: Based on the traditional formula "Pearl pill" and guided by "determination oftreatment based in pathogenesis obtained through differentiation of symptoms and signstheory", a new traditional Chinese medicine (TCM)—compound pearl buccal tablet, whichintend for treatment of pharyngitis (PHY), paristhmitis, dental ulcer, etc. was developed andstudied.Methods: (1) Formulation composition of "compound pearl buccal tablet" was ascertainedbased on the traditional formula "Pearl pill" and "determination of treatment based inpathogenesis obtained through differentiation of symptoms and signs theory". (2)Technology process of "compound pearl buccal tablet" was designed based on formulationcomposition and properties of active constituents, and the optimum extraction conditionswas studied with the orthogonal test of L9 (34). (3) Borneol, one volatile component, wasmade into solid inclusion withβ-Cyclodextrin (β-CYD,β-CD) and different inclusionmethods were compared and screened; optimum inclusion condition was studied withuniform design test; Borneol-β-CYD inclusion compound was identified by differentialscanning calorimetry (DSC), X-ray diffraction, and etc; Molar ratio between host and guestwas investigated using molar gradient method; Characteristics of borneol and itsβ-CYDinclusion compound was compared through dissolution and stability tests. (4) Adjuvants forcompound pearl buccal tablet were screened with hygroscopic rate constant as the index,and stability of compound pearl buccal tablet was investigated, simultaneously. (5) Safetyand effectiveness were evaluated by initial pharmacodynamic and toxicity test, respectively.Results: (1) Compound Pearl buccal tablet was composed of pearl powder, Natrii SulfasExsiccatrs, Borax, Radix Rehmanniae, Radix Glycytthizae, Borneol and Mentholum. (2)Single factor and orthogonal test result showed that the optimum extracting condition was 24 times water as solvent and 3 h twice, under which the active constituents contained inRadix Rehmanniae and Radix Glycytthizae can be extracted most completely and bestantiinflammatory effect can be achieved. (3) Saturated water solution was the mostsuitable method for preparing borneol-β-CYD inclusion compound, and the best inclusioncondition was: X1 (borneol:β-CYD)=6.0(w/w), X2 (temperature)=45℃, X3 (time)=4.0 h, X4(rotary speed)=1000rpm, under which promising yield rate and inclusion rate can beobtained. Borneol-β-CYD was validated by DSC and X-ray, results showed that graph ofphysical mixture was simle overlay of borneol andβ-CYD graph, but characteristic peaksfor drug disappeared in bronel-β-CYD graph, which indicated the forming of new phasel.Solubility at 25, 35, 40℃of borneol were 0.292, 0.286, 0.293 mg/ml, respectively, and thatof inclused borneol were 0.309, 0.317, 0.342 mg/ml, respectively. Solubilization forβ-CYDon bomeol achieve greatest when molar ratio between host and guest was 1:1. Light,thermal and humidity stability tests showed that borneol is more stable in inclusioncompound than in physical mixture. (4) Granulation-forming ability order:lactose＞dextrin＞mannitol＞xylitol, hydroscopicity order: xylitol＞mannitol＞dextrin＞lactose,critical relative humidity (CRH) order: dextrin＞lactose＞xylitol＞mannitol. (5) LD50 forcompound pearl buccal tablet was 20.0 g/kg, which equal to 125 times of human clinicalusage amount, and 95% confidence limit was 17.8～22.6 g/kg. (6) Compound pearl buccaltablet show distinguished inhibition effect on croton oil induced mice ear swell, sodiumcarboxymethycellulose (CMC-Na) induced mice abdominal cavity leukoplania, miceacetic acid induced pain, mice thermal induced pain and phenol induced rat dental ulcer.Conclusion: (1) Glycyrrhizin and catalpol are principal active constituent for RadixGlycytthizae and Radix Rehmanniae, respectively, and they both show good watersolubility. So they can be extacted completely by water-coction extract technology; Ethanolprecipation may decrease catalpol content, and anti-inflammatory effect showed noincrease, so water-coction extract technology is just a good choice. (2) In water, there existsa dissociation equilibrium for borneol-β-CYD, which enable some borneol release from itsinclusion compound. When at a small sample amount, borneol can be released from its inclusion compound completely, since it is below its dissociation equilibrium concentration,and inclusion compound is a kind of amorphous powder; while at a large sample amount,which exceed its dissociation equilibrium concentration and so bomeol release is impeded. (3)Stability for borneol can be improved significantly after inclusing withβ-CYD, whichachives the aim of our study. (4) Lactose is the best diluents for compound pearl buccaltablet. (5) Acute toxicity and intial pharmacodynamics tests demonstrates compound pearlbuccal tablet is safe and effective.
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