Clinical Analysis About The Treatment Of RA With SanShui BaiHu Decocation And The Study About Dosage Form Of SSBH

BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease, the main manifestation of which is of chronic and symmetrical and erosive arthritis. The pathological feature of RA is synovial inflammation, and it could result in joint cartilage and bone destruction, eventually lead to joint deformities. Without regular treatment, about75%of the patients appeared disability within three years. RA is distributed in all parts of the world, the prevalence was0.18%～1.07%in different populations.The prevalence of RA was0.4%, the total number of cases was more than$5million in our country. RA in the age can be onset, peak at the age of30～50year old, general women than men.The pathogenesis of rheumatoid arthritis is not clear, generally associated with genetic, environmental, infection and other factors, these factors how to break the immune tolerance to start autoimmune process is still not very clear, the pathogenesis of RA mainly have the following several kinds of hypothesis, molecular simulation hypothesis, Epitope spreading,fuzzy recognition.The uncertainty of pathological mechanism leads to multiple targets and blindness in the treatment of RA. Although classical immunosuppressive therapy can improve greatly on the condition, even can be achieved clinical cure, but the long-term use of immunosuppressive agent can lead to many side reactions, such as the gastrointestinal of methotrexate(MTX), cyclophosphamide(CTX) and liver dysfunction, leflunomide (LEF) cause irregular menstruation, secondary pulmonary inflammation and skin inflammation, etc, at the same time it also has a plateau on the curative effect. Because of this, the compliance of patients is still very poor. In recent years, investigate of biological agents of cytokine network in each therapeutic targets made more achievements. Since twentieth Century, especially, the biological agents which exemplify tumor necrosis factor (TNF-a) antagonist bring a new revolution for the treatment of RA,it includes etanercept, infliximab and adalimumab,The three TNF-a antagonists can reduce the joint inflammation of RA, reduce the clinical activity of RA and decrease rheumatoid factor (RF) and titers of anti-cyclic citrullinated peptide antibody,and can improve joint function and delay radiological progression the joint, but Biological agents are very expensive,the total effective rate of the three drugs in the treatment of RA was about70%, It has some side effects, it is easy to cause the new immune disorders, and confined by indication, cannot be extended.It had been clearly explained that how and why arthromyodynia happened in the ancient traditional Chinese medicine (TCM).In recent years, the traditional theory of wind-cold-damp-hot was greatly improved and extended. Such as the theory of "kidney deficiency" and "the deficiency,evil,blood stasis", etc. Accordingly,TCM plays an more and more important role in the treatment of RA.Therefore, the issues on how to fully explore the advantages and potential superiorities of TCM, and how to strengthen the research of the effective TCM formula are the key points in the treatment of RA. Since ancient times in China, because of more profound understanding for arthromyodynia, many physicians got experience in respective treatment, also obtained good curative effect, so many patients of RA prefer to choose treatment of TCM. However, a joint application is adopted with disease modifying anti-rheumatic drugs (DMARDs) and anti-tumor necrosis factor TNF-a preparation in many cases. There’s few systematic and scientific research on how to evaluate their joint application of safety, long term efficacy of clinical and radiology.SanShui BaiHu decoction(SSBH) is experience applied by Department of Rheumatology and immunology of the traditional Chinese and Western Medicine hospital of Southern Medical University in the treatment of rheumatoid arthritis for many years, the prescription composed of Radix rehmanniae, Cortex Moutan, S uberect spatholobus stem,18kinds of TCM and combined, with the efficacy of dispelling wind and removing obstruction in the meridians, clearing heat and removing toxicity, promoting blood circulation for removing blood stasis, disperse swelling and relieve pain. At present, SHBH is clinical prescription, mainly used for the treatment of rheumatoid arthritis (RA) active period and inflammatory progression. Performance for the joint swelling and pain, local burning with systemic thermal imaging, Can obviously inhibit the reaction of inflammation, reduce the inflammatory activity index, delay the progress of bone destruction of patients with rheumatoid arthritis. Early, the preparation is the decoction, for the convenience of patients to carry convenient, now change into granules. To ensure the quality of the preparation, convenient for patients to use, preparation craft of SHBH granule was studied, and take the identification with TLC identification method of Radix rehmanniae, Cortex Moutan, Suberect spatholobus stem, etc, the quality control are discussed, which provide the basis for clinical medication.In the clinical observation and animal experiment that was completed, The combined application of SSBH and LEF in the treatment of active RA, it improve the degree of inflammation was significantly better than the use of LEF, and can get better curative effect. SSBH can slow down the platform of the LEF on the treatment, the treatment time combined with LEF is longer, the effect is better. SSBH can accelerate the onset time of RA treatment, increased cortical hormone withdrawal rate. Health assessment questionnaire (HAQ) results also show that SSBH can improve patient’s quality of life. SSBH helps to control the activity of RA and progression of inflammation, but also can reduce the adverse reactions caused by only taking LEF. Animal experiments of CIA showed that, SHBH can control the acute inflammation of CIA. SSBH can also inhibit the synovial hyperplasia, fibrosis, inflammatory cell infiltration, cartilage and bone destruction in the development process of CIA inflammation, but and other TCM of treatment of RA, they lack direct evidence that can inhibit bone destruction in clinic, while we compare long-time imaging data, especially the changes in the hands and wrists joints X-ray, we can be obtained directly the evidence whether SSBH can inhibit the synovial hyperplasia and bone destruction. According to the series studies on the and analysis of usual pharmacological results, The prescription can intervene multiple links reaction of RA immune inflammatory from multi-channel, multi-level. It can not only anti-inflammatory and analgesic, but also suppress the immune, as well as an important part of action is to inhibit synovial fibroblasts proliferation. Professor Xiao Changhong apply SSBH combined with other drugs to treat arthralgia due to heat-toxicity of RA for more than10years, that make sure curative effect, and continue to be improved in the clinical application. But and other TCM of treatment of RA, they lack the evaluation analysis of long-term efficacy the treatment of RA, lack investigate on the safety and efficacy of Radiology, therefore, we needs retrospective analysis of long-term effect of SHBH in the treatment of RA. Chapter I:Retrospective analysis of the long-term efficacy of RA treated with SSBHPurposeThe study is evaluated and compared through retrospective analysis that the long-term clinical efficacy, drug safety and radiology efficacy of the heat tybe of RA dealt with SSBH.Case selectionFrom the patients who visited the hospital rheumatology outpatient department and inpatient department in Southern Medical University of traditional Chinese medicine and Western Medicine in May2012, Established in accordance with the inclusion criteria and exclusion criteria, we choose to meet the case of the requirements.MethodsAccording to whether the patients with Sanshui Baihu Decoction, they that meet the inclusion criteria were divided into SSBH group and Western medicine group.The clinical data of cases were collected, we calculate and record the disease activity of patients before and after treatment(DAS28), relative laboratory indexes (ESR, CRP, CCP, RF), Sharp score of hands and wrists, through the analysis and comparison of the clinical efficacy, we find out the differences of the clinical efficacy of treatment methods of the two groups; To check the patient’s blood, liver and kidney function, chest X-ray, and return visit to the patients, and evaluate the safety of the two treatment methods.ResultsNo significant difference between two groups in gender, age, course of disease, such as comparison, p>0.05, which is comparable to. Two groups both can improve the activity of the disease of RA, SSBH group was slightly better than the western medicine group. The results demonstrated that the application of SSBH was the only western medicine can be more lasting laboratory indices in patients with reduced effectively. Two groups are all failed to prevent the development of bone erosion, radiographic progression between the two groups had no significant difference, the combined application of SSBH may improve the patient’s bone destruction. The SSBH group is better than western medicine group security.ConclusionsThe combined use of SHBH a simple application of DMARDs or (and) the biological preparation that can effectively reduce the activity of RA disease, reduce laboratory index more effectively, can improve or delay bone destruction of patients, in short, it improved the therapeutic effect, adverse reactions are obviously reduced, the safety is improved, so it is necessary to further study. We need more samples, randomized prospective study of long-time. Joint nuclear magnetic resonance (MRI) studies, it can observe subtle changes of inflammation and cartilage destruction in short-term, in order to betterly evaluate the SSBH that play the role in the bone destruction of RA.Chapter Ⅱ:The study about dosage form of SSBHPurposeTo study the preparation and quality standards of SSBH.Materials and MethodsThe extraction process are main factors which influence the water amount, decoction time, Decoction times,3levels for each, Optimum water extraction technology selected by orthogonal test, took extract yield as the evaluation index; Access to relevant literature, decided to use the material and powder equivalent, and then sprayed into the quantification of different concentrations of ethanol, mixed in different time, take the concentration of ethanol, accessories and mixing time as factors of orthogonal test,3levels for each, The best choice of granulating conditions by using orthogonal test method, take particle yield as the evaluation index; Preparation of the sample solution, the control medicine solution and negative control solution,then TLC method was used to identify Radix rehmanniae, Cortex Moutan, Suberect spatholobus stem in the prescription.ResultsThe optimum conditions of water extracting process is A2B3C3, the first supplement water quantity after adding10times amount of water to soak for0.5hours, the rest each plus10times the volume of water, extracting for3times, each time2hour extraction; The optimum conditions of granulation technology is A1B1C3, namely, the addition of95%ethanol and beta cyclodextrin amount, mix15minutes. TLC was specific, and the blank test showed no interference. The TLC results of Radix rehmanniae, Cortex Moutan, Suberect spatholobus stem showed that the sample and the control has a corresponding spot of medicinal materials, while the negative control products with corresponding position without.ConclusionsThe study about dosage form of Sanshui Baihu granules showed that, the SSBH water extraction, particle preparation technology processed is stable and reliable; quality control standard preparation has high sensitivity, strong specificity, that provides the basis for Sanshui Baihu granule toproduct. When it isnecessary, jianqu process of Artemisia annua and asarum be studied deeply, the index components should be added in water decoction process, it namely compound tomacromolecular content, but because of the limited of time and funds, it could not be completed, so we need to further improve the screening complex macromolecules in Sanshui Baihu granules.In granulating factors, P values of three granulating factors are greater than0.05, Therefore, we need to be further screened granulation factors better, improve the granulation process. For clinical prescription composed of18kinds of traditional Chinese medicine, with just three herbs as a quality control standard is not enough, but some component content particles heated easy decomposition, volatilization or and other components of the reaction changes, more quality must also more quality be studied for the SSBH granule, to promote maturity and perfection of the quality control standard. Experiment shows that SHBH granule according to the optimal preparation process conditions to be made is brown, slightly sweet, forming the good, provide the basis for the pilot production of the product.