Shanmugapriya, P (2016) A Scientific approach on the Validation of Santha Santhrothaya Mathirai (SSM) a Siddha Herbo-Mineral Preparation for its Safety and Efficacy in the Management of Hepatic disorders. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
Santha santhrothaya mathirai (SSM) is a herbo-mineral formulation widely prescribed for hepatic disorders. The ingredients of SSM include mercurous chloride, borax, turmeric and lemon juice all of which are said to possess hepatoprotective activity. Although, the medicinal preparations mentioned in Siddha literature are time-tested standard preparations it is need of the hour to document standardization procedures by using sophisticated instrumental analysis to maintain quality control. In the present study the preparation of SSM was standardized initially and then it was scientifically validated by adopting various analytical techniques.Toxicity and pharmacological studies were also performed to understand the safety and efficacy of the traditional drugs. The raw materials used in the preparation of SSM were identified and authenticated using contemperory accepted practice. The raw materials of mineral origin viz., pooram and vengaram were purified strictly following the classical Siddha texts. The study drug SSM was prepared adopting the method mentioned in the “Siddha Vaithiya Thirattu”. In order to standardize the preparation protocol, SSM was prepared thrice (SSM-A, SSM-B and SSM-C) by following the same protocol and the similarity was demonstrated by examining various physical and chemical nature such as total ash, moisture content. The microbial load, aflatoxins and pesticide levels were analyzed and were found to be within the WHO permissible limits in all the three samples. Quantity of heavy metals (lead, cadmium, mercury and arsenic) in all the 3 samples of SSM were estimated by using atomic absorption spectroscopy (AAS) and were found to be within the permissible limits. Total curcumin content of SSM was estimated in all the three samples of SSM by HPTLC analysis. The amount of curcumin present in Sample A was 0.6589 %; Sample B was 0.6884 % and Sample C was 0.7104 %.Total curcumin content of SSM - (A-1.15%,B 1.19%, C1.23%) were analysed by UV spectroscopy. There was no significant variation in the curcumin content in all the three samples of SSM. Since all samples were similar throughout the above analysis one of them was taken for further analytical procedures. TGA analysis of SSM confirms a weight loss of 77% indicating the presence of large quantity of organic organic material in SSM. The chemical changes that have occurred during the Siddha methods of purification process were assessed by using Raman spectroscopy, FTIR, XRD and SEM Analysis. The analytical studies confirm the changes in the chemical structure of raw and purified state. The tetragonal crystalline structure of Pooram (Mercurous chloride) showed changes in its crystalline structure though the exact shape could not be established. Similarly Vengaram (Borax) also showed a change in its structure from rhombohedral form to orthorhombic form. Moreover the presence of organo-mineral complex in SSM can be due to the combination of turmeric with purified vengaram, purified pooram or both. SEM Analysis revealed the particle size of 1μm to 500 nm in various magnifications. Also the morphological structure showed variations in purified and prepared medicine SSM when compared to raw samples. In order to understand the nature of inorganic materials present in SSM, the XRF, ICP-OES and mercury analysis by tituration method was performed. Heavy metals concentration of Mercury, lead, cadmium and arsenic were observed by the ICP-OES. This analysis of raw pooram (P1), raw vengaram (V1) showed mercury level and Sodium level as 123.241ppm and 545.862ppm respectively. There was significant reduction in the content of mercury (55.87ppm) in Pooram and the content of Sodium (203.110ppm) in Vengaram in purified state. Further reduction was observed in the mercury and Sodium level in study drug SSM as 3.154ppm and 125.383 ppm respectively. The other heavy metals such as As, Cd, and Pb were below detectable level (BDL) in all the samples (Raw, Purified and prepared samples). The concentration of elements in oxide form was analyzed through X-Ray Fluorescence in the Raw, purified and prepared samples. The XRF study revealed the addition and deletion of trace elements and a reduction in the percentage of Mercury from 87.23% in raw form to 59.59% in purified form and 58.82% in SSM finished sample. From the results of tituration method, mercury content was also reduced from raw state of ingredients to purified and finished state of SSM. These analytical studies are essential since the raw materials for herbomineral preparations are often sourced from various regions and during various seasons. The present study ensures the quality control of the drug which is essential for the prevention of adulteration, reproducibility, assessment of finished product, estimation of active principle and global acceptance. SSM was accessed for its safety on short-term and long-term administration by performing acute, sub acute, subchronic toxicity in animal models. In acute toxicity study, SSM did not produce any mortality or exhibit any abnormal signs for 14 days even upto the dose of 2000mg/kg, on single oral administration.Gross necropsy of different organs revealed no abnormalities after 14 days.In subacute toxicity study, oral administration for a period of 28 days did not showany behavioural abnormality and mortality even at the dose of 250 mg/kg. Gross pathological examination and histopathological analysis of the various organs such as heart, liver, kidney, lung, spleen, stomach, brain did not reveal any lesions in any of the groups. In subchronic toxicity study, there was no behavioural abnormality and mortality throughout the study period of 90 days except mild laxative effect in high dose group. Few changes were observed in haematological and biochemical parameters of SSM treated animals when compared to control groups but were within the physiological limits. Moreover the reduction of liver parameters ALT and AST reveals the hepatoprotective effect of SSM. Histopathological examinations of the tissues revealed mild inflammatory changes in liver and kidney with no significant changes in AST, ALT, urea and creatinine which are biomarkers of hepatic and renal damage. Recovery group was maintained to assess all the above haematological, biochemical and histopathalogical parameters and were found to have no significant toxicological changes. ICP-MS analysis of renal tissue indicates that the study drug SSM does not cause any cumulative toxic effect in renal tissues as the levels of mercury was below the detectable limit in post retrieval group. The results of the toxicity study confirms the safety of SSM towards human consumption. The pharmacological activity of SSM was accessed using three different animal model that represents Paracetamol - induced liver injury, LPS +D–galactosamine induced hepatoxicity which may mimic alchohol induced liver damage, acute liver damage and viral hepatitis respectively. In all the three models, SSM was found to reduce various liver function parameters such as AST, ALT, ALP, Urea and bilirubin that were elevated due to disease induction. Moreover, SSM also increases the total proteins in all the three pharmacological models. Furthermore, treatment with SSM at the dose levels of 25 and 125mg/Kg significantly increases the hepatic antioxidant enzymes such as SOD, CAT, GRD, and GPx and decreases the level of lipid peroxidation when compared to the disease control groups. Histopathology analysis of liver showed that SSM at Low (25mg/kg) and high (125mg/Kg) doses greatly reduced the level of fibrosis and deposition of collagen fibres in alchohol induced liver injury and paracetamol induced liver injury as almost equal to the standard drug Liv 52 and the levels of fibrosis and restoration of collagen fibres in D-Galactosamine induced liver injury were almost similar to that of the standard drug Silymarin. Over all SSM was found to contain notable quantity of mercury in the form of organometallic complex. But it was found to be effective in the management of liver disorders and was experimentally very safe even at very high doses. This study clearly demonstrated the traditional mercury containing drugs are safe for oral administration plausibly may be due to the traditional purification and preparation protocols employed during the process of formulation. CONCLUSION: It is concluded that the trial drug SSM a classical Siddha formulation, was well formulated ensuring the quality by complying with the GMP and GLP standards at every step right from procurement, authentication ,purification to final product analysis. The toxicological profiling of SSM reveals that it has a large margin of safety on acute, sub acute and sub chronic toxicity in experimental rats. Also the pharmacological studies on SSM has proved it to be hepatoprotective and efficacious in the therapeutic dosage for treating liver diseases. The reverse pharmacological work to re-validate the traditional formulation, SSM confirms the safety profile and effectiveness by adopting the modern scientific and acceptable methods to satisfy the present day demands. Hence through this work, an effort has been made to bring out SSM as evidence based safe Siddha medicine for Liver disorders.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Scientific approach, Validation, Santha Santhrothaya Mathirai (SSM), Siddha Herbo-Mineral Preparation, Safety and Efficacy, Management, Hepatic disorders. |
| Subjects: | AYUSH > Nanju Noolum Maruthuva Neethi Noolum |
| Depositing User: | Subramani R |
| Date Deposited: | 14 Jan 2020 17:54 |
| Last Modified: | 15 Oct 2022 13:19 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/11839 |
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