| BackgroundHyperthyroidism is general term for a group of diseases that several etiologies caused thyroxine excessive which leaded to the system such as nerve, circulation, digestion excitability increased and metabolic hyperfunction, it's a clinical syndrome. Hyperthyroidism's common symptom is the more one eaten, the easier hungry, weight loss, tachycardia, fatigue, impatience, excitable, etc. The etiology of hyperthyroidism is complicated, and the exact pathogenesis is unclear too. The most common symptom is Graves's disease which accounts for about 85% of all patients with hyperthyroidism. Secondly common symptom is tuberous strumous with hyperthyroidism and subacute thyroid inflammation with hyperthyroidism. Chinese medicine theory considered that the simple goiter is hyperthyroid many areas. It is generally acknowledged that the causes of this diseases is ferrite Yinkui, kidney Yin deficiency, Yin deficiency an Yang excess of the patient, with the addition of gentle disposition disorders, therefor it became born hyperactivity of fire due to Yin deficiency, Qi-Yin deficiency, block phlegm, and so on. The lesion location of hyperthyroidism involved liver, kidney, lung, spleen, heart, mainly in liver and kidney.It mostly used anti-thyroid medication, radioactive iodine and operation, and so on in modern medicine. The effect of anti-thyroid drugs was inhibited thyroid synthetic thyroid hormone. The two latter measures were through destroyed thyroid organization and reduced thyroid hormone production to achieve therapeutic purposes. But all of the three can't treat the causes of hyperthyroidism. And it's easily happened adverse reactions such as granulocytopenia, exanthema and liver damage.Over the past 10 years Chinese medicine treatment of hyperthyroidism has been encouraging progress. The emergence of new treatments for prescription and the improvement of the methods for treatment which shows the unique advantage in improving hyperthyroidism symptoms and regulating the body's immune system, it also increased clinical curative effect and reduced adverse reactions and the recurrence rate. Chinese medicine treatment has been come under recognition by Chinese and foreign researchers because it for same degree revealed the mechanism of Chinese medicine treat hyperthyroidism. The increasing researches suggested that traditional Chinese medicine will play an important role in prevention hyperthyroidism.Yinning tablets are a result of on-chip Guangzhou Hospital of the South side of clinical experience. It is based on theory of TCM (traditional Chinese medicine) and through the modern technology, screened hundreds of Chinese herbal medicine from pharmacology, pathological science perspective. Yinning tablets were composed of nine traditional Chinese medicines such as astragalus, Kunming mountain hitom, turtle shell, angelica, rehmanniae and liquorice. All of these medicines altogether had nourishing yin, softening hardness, detoxifying and resolving efforts. The clinical observation suggests that Yinning tablets had a better clinical effect on Yin-deficiency, phlegm-damp and blood stasis hyperthyroidism. It can effectively eliminate hyperthyroidism symptoms, fast repair the normal function of each system, improved their immune function, in order to cure this disease. And the preliminary experiments showed that Yinning tablets can protect the liver and avoid of anti-thyroid drugs caused liver damage. It filled the treatment drug blank of treat hyperthyroidism and protected liver at the same time.This research will combine multidisciplinary research methods an techniques such as pharmacy, natural medicinal chemistry, pharmacology, endocrinology, nuclear medicine and health statistics. It will be focusing on the best technical condition to produce Yinning tablets with orthogonal test and pharmacological effects of Yinning tablets on the mice with Yin-deficiency hyperthyroidism. It will provide the evidence for the new drug research and development and clinical hyperthyroidism treatment finally.PurposeTo optimize the preparation technique of Yinning tablets with orthogonal test and selected the best preparation technique conditions of it, and it will provide the evidence for the new drug research. To establish the model of hyperthyroidism with Yin-deficiency by fed mouse with thyroid and reserpine. To observe- the pharmacological effects of Yinning tablets on the mice with Yin-deficiency hyperthyroidism, the appearance, eat and drink intake, weight, thyroid and liver organ index, the content of cAMP and cGMP, atmospheric anti-anoxia survival time, loaded swimming time and hepatic glycogen content of each group would be tested and analyzed. It will provide the evidence for the new drug research and development and clinical hyperthyroidism treatment finally.Methods1 The research of optimizing the preparation technique of Yinning tablets with orthogonal test First of all was a preliminary study to optimize the extraction times with the extract rate as optimization target. According to the pre-experimental results it selected 3 factors of adding water, decoction time, soaking time, and the 3 level of each factor were adding water(12,10,8times), decoction time(3-3-2,3-2-2,3-2-1h), soaking time(1.5,1.0,0.5h) respectively. The next to optimize the preparation technique of Yinnning tablets with extract rate, astragaloside content and epicatechin content as optimization target through orthogonal test. It will optimize the best preparation technique of Yinning tablets through intuitive analysis and variance analysis and verify the optimal preparation process. Astragaloside content and epicatechin content were all determined by HPLC. 2 Thyroid and Reserpine-induced Hyperthyroidism Yin-deficiency Model of Mouse48 Kunming mice separate male and female were randomly divided into four groups, each with 12. The first group was the control group,2 to 4 were the experimental drug-treated group, including thyroid and reserpine-low, medium and high-dose group. In addition to the first group lavage volume of saline, the other groups were given the concentration of 75mg/kg thyroid and 0.5mg/kg reserpine, 150mg/kg thyroid and 1mg/kg reserpine,300mg/kg thyroid and 2mg/kg reserpine saline suspension.1 times/d, it will continue doing this 7d. Observe the appearance, weight of each group, determine the value of serum T3, T4, FT3, FT4, TSH, and take the thyroid, liver tissue for weighing to calculate the organ indexes. 3 The pharmacological effects of Yinning tablets on the mice with Yin-deficiency hyperthyroidismKunming mice were randomly divided in 6 groups of 10 according to the administration on an empty stomach weight and evenly male, namely:control group, hyperthyroidism model group, positive control group (graves ling group), Yinning low-dose, medium and high-dose group. In addition to the control group, the other groups were given 300mg/kg thyroid and 2mg/kg reserpine saline suspension for 7 days to establish the mouse model of hyperthyroidism Yin-deficiency. Graves ling group were given 1.2g/kg graves ling suspension, and Yinning low-dose, medium and high-dose group were given 0.6g/k,1.2g/k,1.8g/kg yinning suspension(equivalent to 10 times of the clinical dose,20 times,30 times) once a day from the first eight days. The mice in each group were observed their normal situations, thyroid and liver organ index, the content of cAMP,cGMP,atmospheric anti-anoxia survival time, loaded swimming time and hepatic glycogen content. Measure the weight of each group before the model, the 7 day of the model and 30 days for treated.Results1 The research of optimizing the preparation technique of Yinning tablets with orthogonal testThe results of preliminary study indicate that the third time extract rate is more than 3 times of 10% of the total amount, and except the amino acids can't be detected, the saponins and tannins can be detected and the results were obvious. Therefore, the extraction times were three times for sure. The results of orthogonal test indicate that factor A should choose A1 which is 12 times of adding water. Factor B had no significant effect on extract rate, but had significant effect on astragaloside content and epicatechin content, so it should choose B2 or B3 that decoction time is 3-2-2h or 3-2-1h considering the two after evaluation index were more important. Factor C had no significant effect on extract rate, but had significant effect on astragaloside content and epicatechin content, but it's more unimportant than factor B, so it should verify the B] and B2 further considering-the production cost and production time. So the best preparation technique of Yinning tablets was A1B2C1 or A1B2C2 according to the orthogonal test results. This study finally determined the best preparation technique of Yinning tablets was A1B2C2 through the verifying test and repeat experiments. The technique is adding water 12 times, decoction time 3-2-2h, soaking time 1.0h. And this technology is reasonable and practicable.2 Thyroid and Reserpine-induced Hyperthyroidism Yin-deficiency Model of MouseThe results of this study indicate that the mice of each group were given thyroid and reserpine suspension for 7 days, compared with the control group, the Group 4 mice serum T3, T4, FT3, FT4, TSH values and weight were significantly higher (P< 0.05), serum TSH was significantly lower (P< 0.05), organ indexes of thyroid and liver were significantly higher (P<0.05) with clinical manifestations of traditional Chinese medicine such as restless, fur without burnish, water reduction. Group 4 mice modeling was success. It's dose choice for 300mg/kg thyroid and 2mg/kg reserpine saline suspension.3 The pharmacological effects of Yinning tablets on the mice with Yin-deficiency hyperthyroidismThe results of this study indicate that the Yin deficiency models of mice were made with thyroxine and reserpine and treated for 30 days, compare to the hyperthyroidism model group, the weight, content of cGMP,atmospheric anti-anoxia survival time, loaded swimming time and hepatic glycogen content of Yinning low-dose, medium and high-dose group were significantly increased (P<0.05), thyroid and liver organ index, content of cAMP, the ratio of cAMP and cGMP were significantly decreased (P<0.05)Conclusion1 This study selected the best pharmaceutical technology of Yinning tablets which was A1B2C2(adding water 12 times, decoction time 3-2-2h, soaking time 1.0h). This technology is reasonable and practicable which can save the resource, reduce the producing cost as well as improve the economic efficiency.2 Through the determination of indicators of mice, this study confirmed that administration of 300mg/kg thyroid and 2mg/kg reserpine saline suspension for 7d, the hyperthyroidism Yin-deficiency mouse model was successful. 3 Through the determination of indicators of mice, this study confirmed that Yinning tablets can improve the symptoms and their anti-hypoxia and anti-fatigue capability of the mice with yin-deficiency hyperthyroidism, and had an effect on yin-deficiency. |
PDF Full Text Request