Veerasivaraman, M (2018) Preclinical Safety Evaluation of Rathi Nagara Rasa Mezhugu. Masters thesis, National Institute of Siddha, Chennai.
|
Text
320618318veerasivaraman.pdf Download (12MB) | Preview |
Abstract
Preclinical safety evaluation of Rathi nagara rasa mezhugu (RNM) was carried out for dissertation. The drug was chosen from the Siddha literature Anuboga vaidhaya navaneedham. The ingredients of Rathi nagara rasa mezhugu are metallic and herbal compounds like Rasam (Mercury), Ganthagam (Sulphur), Serankottai (Semecarpus anacardium). It cures the disease of Lingaputtru (penial cancer), Algulputtru (Cervix cancer), Araiyaappu (Adenitis), Kandamaalai (Cervical adenitis), Karunkuttam, Senkuttam (Leprosy), Megaranam (Syphilis), Kaalkai mudakku (Rheumatoid Arthritis). The raw drugs were procured from reputed raw drug shop, Broadway, Chennai and the drugs were identified and authenticated by dept. of Gunapadam, and by the Botanist, National Institute of Siddha, Chennai. The ingredients were purified and the medicine was prepared as mentioned in the Siddha literature. Rathi nagara rasa mezhugu was underwent physicochemical, phyto- chemical, biochemical analysis, heavy metal analysis by using ICP-OES, and particle size analysis by using HR-SEM. Acute and Repeated oral 28 day toxicity were conducted as per the OECD guidelines 423 & 407 respectively. In Rathi nagara rasa mezhugu, the loss on drying at 105oC was found to be 1.98%, it falls in between the limit range (1-20%). So the determination of moisture content shows the good stability of the drug test drug. The total ash in the test drug was found to be 2.09%, and the acid insoluble ash to be 0.7%. Both types of ash values were within the limits. The minimal level of acid insoluble ash shows the less extraneous matters that indicate the purity of the drug RNM. The water soluble extract value of Rathi nagara rasa mezhugu is 3.77% and the Alcohol soluble extractive is 15.59%.As the test drug has more alcohol soluble constituents than water soluble, it would be non-polar. So the drug will have good bioavailability &intracellular distribution without possible accumulation inside the cells. The poor water solubility may prolong the duration of the drug action. The pH of RNM was found to be 4.65 which means it is weekly acidic and safe for oral administration. Bio Chemical Analysis of RNM indicated the presence of carbonate, calcium, magnesium, potassium, aluminum, iron, zinc, mercury, and alkaloid. Phytochemical investigation to detect the presence of phyto constituents in formulation RNM reveals the presence of glycosides and fixed oil and fat. The Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) of RNM results showed that the Heavy metals like Mercury (03.214 mg/L) was found within the permissible level in RNM. Hence it may be safe for human consumption. It also shows the presence of physiologically important minerals like sodium, potassium, iron, zinc, Calcium, phosphorus. Some Heavy metals shows below detection level are Aluminum, Arsenic, Copper, Lead, Magnesium, and Nickel (Table.5). HR-SEM analysis of Rathi nagara rasa mezhugu showed difference in size and reveals the particle size as 1.0 - 2.0 μ. The particles in RNM had even distribution with agglomeration of particles due to reported grinding. Hence the drug may have increased absorption. In Acute Oral Toxicity study four different dose (50, 2000mg /kg.b.wt) of Rathi nagara rasa mezhugu were administered stepwise (step up) manner. Throughout the 14 days of observation period, no mortality and signs of toxicity were observed in RNM treated groups. The results of the Acute Oral Toxicity study indicate that the LD50 of RNM is more than 2000 mg/kg b.wt. So the drug RNM comes under the category 5 as per GHS (Globally Harmonized System of Classification). In the 28-days repeated dose oral toxicity study, there were no mortality and morbidity in all Rathi nagara rasa mezhugu treated groups. Food and water consumption of the animals is significantly differed When RNM treated drugs compare to control group (Table7,8& Figure2,3). But they are within physiological limit, and this study reveals that it does not adversely affect the basic metabolic processes of the experimental animals. Body weight of the animals is significantly differed When RNM treated drugs compare to control group (Table9, 10 & Figure4, 5). But they are within physiological limit. The results of hematological investigation, reveals no significant changes in all RNM treated groups as compared with the control groups except for total differential count, hematocrit but the values are within the normal physiological limit. The results of biochemical investigations, in test groups there was significant changes present in VLDL Mid dose, when compared with the control group. But the values were normal biological limits. The result of liver function test and renal function test, reveals no significant changes in all RNM treated groups as compared with the control groups. No abnormality was observed in histopathological examinations of all organs in RNM treated groups as compared with the control groups. So the ‘No Observed Adverse Effect Level’ (NOAEL) of Rathi nagara rasa mezhugu may be greater than 468 mg/kg b.wt in Repeated Oral 28-day Toxicity study. CONCLUSION: From the results of this analytical evaluation of the test drug Rathi nagara rasa mezhugu (RNM), it is inferred that quality and stability was good when prepared under the standard protocol mentioned in this study. Qualitative analysis of RNM reveals the Purity and Bioavailability of the drug As heavy metals were found to be within the permissible limit .so the drug is safe for oral consumption. The particulate size of the test drug was determined by SEM analysis. In vivo toxicity study reveals the drug RNM shows no mortality and signs of toxicity up to 2000 mg/kg.b.wt in acute oral administration. In Sub acute toxicity study there was significantly changes in hematological, biochemical parameter in RNM treated groups when compared to control group but the levels were within physiological limit. The histopathology report also confirms that there are no remarkable cellular changes at all the dose levels. And No Observed Adverse Effect Level (NOAEL) high dose level (468 mg/kg b.wt), which is ten times that of therapeutic dose.. Based on these results it can be conclude that, the dose level of Rathi nagara rasa mezhugu 3 to 4 kundri twice a day mentioned in the Siddha literature Anoboga vaithya navaneetham is safe dosage for human consumption. In future it is to be carried out to study the pharmacological activity and clinical trial to prove the efficacy of the drug.
| Item Type: | Thesis (Masters) |
|---|---|
| Additional Information: | (Reg.No.321516207) |
| Uncontrolled Keywords: | Preclinical Safety Evaluation ; Rathi Nagara Rasa Mezhugu. |
| Subjects: | AYUSH > Nanju Noolum Maruthuva Neethi Noolum |
| Depositing User: | Subramani R |
| Date Deposited: | 29 Dec 2018 10:44 |
| Last Modified: | 29 Dec 2018 10:44 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/10284 |
Actions (login required)
 |
View Item |
