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Psoriasis is a kind of chronic inflammation with plaques and scales, influenced by varieties of reasons. Its symptoms’severity varies from small plaques locally to areas all over body. It is repeatable and hard to cure, it influences2%-3%of the total population on earth, being one of the most common autoimmune diseases. Psoriasis affects all regions of the world, being the most common immune-mediated skin disease in adults in North America and Europe, affecting about25million people. In China, the prevalence of psoriasis is0.123%, which is more of men than women, the North than the South, the urban than rural areas. The incidence in African countries is relatively low. Psoriasis has significant difference not only in race and gender, but also in geography and season. The incidence in Alpine areas is significantly higher than in warm regions, and the Symptoms are aggravated in winter and spring, relieved in summer.Psoriasis on modern research is considered autoimmune diseases with abnormal T cells in the polygenic background. The research and argument about the action of keratinocytes, T cells, neutrophils, and nerve cells on psoriasis and their complex reactions constantly reveal its pathogenesis, to promote the development of medical science, but also to push people to find a more effective anti-psoriasis drug to provide support for the development of human beings.Psoriasis is treated according to its severity by four kinds of drugs, such as topical medicines, light therapy method, traditional oral medicines and new biological preparations etc. If topical medicines and light therapy method doesn’t act on psoriasis, the whole-body drug should be used. Traditional oral medicines conclude vitamin A substances, methotrexate, cyclosporine and acitretine etc., they take effect and have advantages of simple using method and low price, but disadvantages of heavier toxicity in livers, kidneys and bone marrow with teratogenicity, and so restricted usage. Compared with traditional systemic drugs, biological agents can specifically target immune systems and have a better safety and tolerability, fit for a longer-term treatment of psoriasis. Six biological agents have been approved in Europe and America for psoriasis. One class of them targets to T cells related to psoriasis’ mechanisms, but its usage has been decreased because of its weak effect. The other one-TNF inhibitor is the first-line drug for moderate to severe psoriasis, but it is expensive for ordinary patients and its safety is limited.Quite a lot of therapies by traditional Chinese medicine exist, accordingly many prescriptions appear, Qingdai capsule, Tripterygium tablets, Danshen injection, Qing Kai Ling Injection have been widely used in clinical applications and got reliable good efficacy.But, because of the active ingredients of traditional Chinese medicine are not clear, and usually one single indicator is assayed in their quality control in Chinese Pharmacopoeia, which cannot reflect the inner quality entirely and objectively, not fit for the holistic characteristics of traditional Chinese medicine, so limited to be used, and is not in line with the characteristics of Chinese medicine holistic, there are certain limitations. Chinese medicine products’ quality and safety evaluation is not perfect, and can not achieve the aim of stable and controllable quality, so they have not been recognized by the international mainstream drug market.Due to psoriasis’ intractabilities and its special defects, Chinese medicine treatment of psoriasis has broad research space. In basic research, the study of Chinese medicine inside and outside action mechanisms on psoriasis should be deepened, parting of experimental animal models should be established, the classification criteria and laboratory observation indicators should be unified, and their pharmacological action mechanisms should be clarified. Thus, through a comprehensive and systematic experimental study, based on theory of differentiation of symptoms and classification of syndrome together with laboratory index, to explore monome of chinese herbs or compound preparations with definite effect, searching for useful target, and to clarify its action mechanisms is the main direction of the Experimental Study of Chinese medicine treatment of psoriasis in the future.For psoriasis’ characteristic and the research status of its drug, it is significant for psoriasis’ treatment to developing more Chinese herba preparations, promoting the related data and exploiting its advantages of weak side effects, together with improving level of quality control and casting away the disadvantages of violation of herba’s assessment level and integrity.Through recognitions to psoriasis and the learning of Dictionary of Traditional Chinese Medicine, we carried out the study of drugs YXD09for psoriasis, such as its prescriptions, process, quality control method, pharmacodynamics and its pharmacokinetics.(1) The prescriptions of YXD09The prescriptions of YXD09are based on Dictionary of Traditiongal Chinese Medicine, and the knowledge of psoriasis’ characteristics and mechanisms.(2) The preparation optimization of YXD09We choose orthogonal test on L9(34) design with reflow time (A), reflow cycles (B), ethanol concentration (C), the amount of ethanol (D) for factors, emodin for indicator. Taken one-tenth of prescriptions’weight,9shares, after orthogonal test, the extract by ethanol is filtrated and the emodin content is measured by HPLC.The results indicate that the range of factors that affect the optimum process is: ethanol concentration> reflux time> reflux times> the amount of ethanol, and the optimum parameters:C3A2B2D2. Analysis of variance showed that the four process factors were not significantly different (P>0.05). Thus in the practical production, in order to reduce production costs, shorten the production cycle, the reflux time is set at2hours instead of4hours. Thus, the final choice of YXD09’s optimization condition is A1B2C3D2, which is refluxing for2hours,2times, with80%ethanol in8times of the drugs’ amount. Choose rhubarb, Rumex and Polygonum cuspidatum and other herbs to examine the influence of the combined and separate extract to emodin content. The result of the combined and separate one is shown to be162.78ug/ml and161.22ug/ml respectively. Analysis of variance with EXCEL software shows P>0.05, the two extract methods have no significant difference in content of emodin.(3) The quality control method studyBy the thin-layer chromatography, qualitative analysis of emodin and Angelica in YXD09is done. According to thin-layer chromatography (Chinese Pharmacopoeia2010edition is an appendix VI B), drawing10μl of the test solution, reference solution and negative control solution respectively, applying them on the same silica G plate with petroleum ether (30℃-60℃)-ethyl formate-formic acid (15:5:1) as developing agent, after spreading, it is taken under the365nm UV lamp to examine. The method shows the advantages of simple operation, good reproducibility, obvious effect, so can be used as TLC standard of YXD09.Emodin in YXD09is measured by high-performance liquid chromatography. HPLC conditions are like that, Column:ZORBAX Extend-C18(4.6mm×150mm,5um) column; mobile phase:0-6min, methanol:water (40:60);6-20min, methanol: water:0.1%phosphoric acid (75:10:15), gradient elution; flow rate:1.0ml/min; detection wavelength:254nm; column temperature:35℃. HPLC determination value of emodin of three batches of YXD09is166.83μg/ml,172.52μg/ml,160.43μg/ml, and the RSD value is1.7%,1.3%,1.1%, respectively.The above-mentioned method first use thin-layer chromatography to qualitatively analyze rhubarb and angelica of YXD09, and adopt an effective method which is high-performance liquid chromatography to determine the emodine in rhubarb, with advantages of the qualitative and quantitative analysis supplementing each other, comprehensive, reliable and exclusive, and can be the quality control standards of YXD09.On the other hand, the simultaneous assaying of Emodine and Osthole has been studied.(4) The pharmacodynamic study The test is to use mouse vaginal epithelial cells as the model to study the effects of YXD09on mitosis of it.30health female mice from Kunming after successful modeling are randomly divided into three groups, with each group of10mice, respectively:YXD09group, the positive control group, model group; another randomly selected10without modeling as blank test group. The test period is7days. On the7th day, the drugs are administered:YXD09group is perfused5minutes each; the blank group, model group, by the same method is perfused with lOmL/kg of saline each; the positive control group is evenly coated with a layer of0.02%propionate clobetasol ointment in its vaginal wall.1h after the last dose, the mice in each group is treated by intraperitoneal injection of colchicine of15mg/kg to stop its mitosis at the mid age of cell division. Samples are fixed in10%formalin solution, paraffin-embedded, HE stained, counted under the ordinary optical microscope. The results show that YXD09can inhibit mitosis of mice vaginal epithelial cells in estrogen cycle, the effect close to propionate clobetasol ointment (P>0.05).The test also uses mouse-tail scaly epidermis as model to examine the effect of YXD09on forming of its granular layer.30health female mice with similar weight, are randomly divided into three groups, with each group of10mice, respectively: YXD09group, the positive control group, blank group, male and female half and half. The test period is7days. Smearing correspondent drug to YXD09group, while the positive control group treated with propionate clobetasol ointment,and the blank by saline. Mice are sacrificed on the7th day, take the tail’s back-skin2cm away from the root, fixed in10%formalin solution, paraffin-embedded, HE stained, placed under ordinary optical microscope to examine forming of granular layer on scales. The results showed that the granular layer proportion of positive control group, YXD09group are significantly increased (P<0.01), respectively,70.1%,116.1%. Effect of YXD09is significantly superior to that of propionate clobetasol ointment (P<0.05).These results suggest that the the YXD09may inhibit the excessive proliferation of epidermal cells and to promote epidermal cells cutin to achieve the purpose of inhibiting psoriasis, and has broad prospects in the clinical application.(5) The pharmacokinetic study Using SD rat’s abdominal skin as model, by HPLC to determine cumulative transit and skin retention rate of emodin in YXD09per unit area, the vitro pharmacokinetic is studied. Adopting Franz horizontal diffusion cell with volume of3.5ml, the effective diffusion area of1.13cmz, heating by constant temperature water bath to control the temperature at about32℃, the rotational speed of250rpm, accept medium of30%PEG-saline after bubbles’ excluded,3.5ml YXD09solution is added to the diffusion cell. Sampling lml respectively in1,2,4,6,8,10,12,24h after0.22μm membrane filtration, the filtrate obtained, determination of cumulative transit and skin retention rate of emodin per unit area. The results show equation of vitro transdermal delivery of emodin is Q=0.338t-1.411(R=0.9972), with24h cumulative permeation amount of6.76μg/cm2, skin retention of19.10μg/cm2, indicating that emodin zero-order kinetics in YXD09’s penetration through the skin.
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