| A drug quality standard for quality research and development is one of the key elements in the drug research and development. Due to make drug safe and effective, during the development process for its quality system, we should conduct in-depth researches to develop scientific, reasonable and feasible quality standards in order to control the quality of drug.In comprehensive, targeted quality research, limits to control product quality, develop reasonable and feasible is very important, and the quality methods could be reflect the characteristics of the product. Effective control of the quality of the product can verify the stability of the drug production process. Quality standards limit is usually based on two aspects, including safety and efficacy. We should not only pay attention to the safety and efficacy of the quality standards, but limitation should also be noted. General requirements determined in the process of development of quality standards, referencing to the current edition of the "Pharmacopoeia of the People’s Republic of China ", and other countrie’s Pharmacopoeia. Initially, identified on the basis of the test or literature analysis methods, accurate, sensitive, simple, and rapid method for determining the principles of quality standards used in the analysis method validation, but also guaranteed to develop the analytical method has some the applicability and reproducibility, we should even consider the bulk drugs and formulations quality standards in order to set up the project for the characteristics of the product itself, thus ensuring quality in the production and storage when changes occur in the transport process of the products, the quality standards developed sensitively reflect the changes in the quality of this drug. This thesis mainly includes a system research on quality of lipoic acid sustained-release tablets and siliping capsules.Peripheral neuropathy (DPN) is the most common chronic complications of diabetes. Its shows that patients with DPN prevalence rate25%-60%according to our statistics. Currently, considered in the pathogenesis of diabetic neuropathy, a very important part of hyperglycemia excessive rise in the level of oxidative stress within the tissue cells, resulting in a series of cell dysfunction, including vascular endothelial cells and neuronal damage. Lipoic acid is a biologically active natural product, known as the "universal antioxidant". It has the ability to scavenge free radicals, regeneration antioxidants attenuated oxidative stress, accelerate the speed of nerve conduction, repair nerve defects, neuropeptide Y, nerve growth factor and substance P to return to normal, thus it can alleviate or eliminate DPN neuropathy symptom seffectively. In summary, lipoic acid in the treatment of diabetes and its chronic complications shows its unique advantages and would be concerned to be the hot of the diabetes medication!There are foreign pharmaceutical companies to produce lipoic acid preparation of sustained release tablets, but in China, the the domestic formulations species in addition to injections, capsules, soft capsules, ordinary tablets, but not reflected in the sustained-release formulations developed and approval of the relevant literature and information. SFDA approved market-oriented production of lipoic acid formulations can not effectively maintain a stable blood concentration due to the half-life of Lipoic acid is only0.5h approximately. So there is an urgent need to study the development of a suitable oral dosage form, in order to maximize its efficacy. Sustained-release tablets preparation process is maturing, unique release technology preparation lipoic acid sustained-release tablets, the main release medicine slowly in the body, a smooth plasma concentration, half-life, long to be able to maintain effective blood concentration, reduced medication number of times, so that the plasma concentration is relatively stable, low to cause side effects; while the body of oxygen free radicals and oxidative stress is the long-term sustainability of maintaining a stable and effective plasma concentration and conducive to achieve therapeutic effect. Thus, the research and development of lipoic acid controlled release formulations has important scientific significance.lnsomia is a kind of dyssomia syndrome. It refers that one has difficulty to begin or maintain sleep, which resulted in poor sleep quality. So it could hardly satisfy individual’s physiological need and obviously afrect patient’s daytime activities. It is a kind of diseases which characterized as being unable to acquire normal sleep frequently. It is mainly represented as insufficient hours and depth of sleep, and being unable to allay tiredness, restore physical strength and stamina. Slight disease represents as having difficulty to fall asleep, or poor sleep quality, festless sleep, or hardly falling sleep again after being awake. Severe disease represents as pemoctation. Insomia is a common disease in clinic. Its incidence rote accounts for about20%-30%among crowd.Though it doesn’t belong to dangerousdisease, it always encumberspeople’s normal work, living, study, and health.Nowadays, there are a lot of methods and medicine to treat insomia all over the world, but we still have not find a wonder drug which is quick, highly effective, and without side effect Though curative effect of sedative and hypnogenic western medicine positive, it has severe poisonous side effect after long-term using. Furthermore, it is easily to induce dependence and drug resistence to this kind of medicine, so it is easy to cause iatrogenic diseases. Therefore, it has important clinical significance to continue the searching for safe and effective medicine method to treat insomia. Through regulating function of entrail, qi and blood in human body, traditional Chinese medicine may constantly improve sleep state obviously. It will not cause medicine dependence, and will not even induce iatrogenic affection. So it is welcome by patients. Siliping capsule is one of our hospital TCM based on traditional herbs meet unexpectedly selected. This capsules with a lot of advanced made into the clinical insomnia medicine oral dosage forms by scientific compatibility including seaweed, Ganoderma and lucidum Semen. A variety of herbs work together, in order to ameliorate sleep and improve sleep quality.Objectives:1. Lipoic acid, known as the "universal antioxidant", is a biologically active natural product. Taken the new discoveries gether and in-depth understanding of the biochemical mechanisms of lipoic and the clinical application of research and founding, lipoic acid has a unique priority in the pharmacological treatment of diabetes multiple peripheral neuropathies. But the half-life of it is only about0.5h. And the approved market-oriented production of lipoic acid formulations by SFDA could not maintain a stable blood concentration effectively. The first part gave a detailed study on quality standards of lipoic acid sustained-release tablets. Tablets can maintain the steady state plasma concentration, extend the time of drug action, reduce delivery times, and improve compliance of patients. Aiming to improve the therapeutic effect and safety and degrade the peak valley phenomenon of blood drug level, this experiment focous on researching the lipoic acid sustained-release tablets to increase the clinic preparations of lipoic acid.2. Insomnia is a common clinical disease with a long duration and a serious harm, which has a severe impact on our health and daily life. Siliping capsule is our hospital clinical oral medicine preparations for insomnia, which was scientifical compatibility for the seaweed, ganoderma lucidum and suanzaoren extract. These drugs play a role together to improve sleep quality. The second part gave a detailed study on the quality standards of Siliping capsule in order to control the quality of drugs, ensure their safety and effectivity.Methods:1. To prepare the lipoic acid sustained-release tablets which can sustained release for12h, several characters of lipoic acid were examined before prescription, including formulation and design, quality standard, the influence factors for the in vitro dissolution. Orthogonal experimental design was employed to optimize the formulation. Based on the optimized prescription, we studied various factors such as preparation technology, dissolution media, pH, the methods of dissolution determine and rotational speeds. According to the relevant provisions of the tablet general rules on preparations in the Chinese Pharmacopoeia2010Edition (VolumeⅡ), initial development of quality standards were set up. We checked up the items on the quality standard of three batches of semi-works production. It laid foundation for a good preclinical research for the application of new drug and industry manufacture.2. Based on the Chinese Pharmacopoeia2010and the health food registration (provisional)(19th) requirements combined with the quality of work and stability tests of information quality standards, I drafted the descriptions. Quality standards established by the name, manufacture, characteristics, identification, examination, determination, functions and indications, dosage and usage, size, storage and other projects. The characters of appearance and color were identified by microscopic (semen ziziphi spinosae) and TLC (Ganoderma lucidum, semen ziziphi spinosae) received two through ultraviolet spectrophotometry measuring the content of polysaccharides in the prescription.Results:1. The formulation of lipoic acid sustained-release tablets were optimized, which can effectively control the drug release rate. HPLC determination of content was established for quality control, and the results showed that this method had advantages such as good prescision and high recovery rate, which can provide an effective analytical tool for quality standards.2. The Siliping formulation was determined.The characteristic of the TLC spots were noted and TLC identification chrysophanol exhibited good specificities without the interference form negative samples. A good linear range was shown over the concentration range of4.507-15.773μg/ml(r=0.9999). The recovery was101.8%with RSD2.74%(n=6).Conclusion1. The preparation techniques of lipoic acid sustained-release tablets are reasonable and preatieal, the quality of the product is stable and eontrollable. 2. The method of the quality criterion for Siliping capsules is simple, rapid, reliable and accurate which can be used for measuring drug effective components qualitatively and quantitatively. In short, the preparetion was succeded. |
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