Evaluation of Safety and Efficacy of a Poly Herbal Formulation Adathodai Chooranam in Iya Eraippu Noi (Bronchial Asthma)

The aim of the study is to estimate the clinical efficacy of a poly herbal formulation Adathodai chooranam in the treatment of Iya Eraippu Noi (Bronchial Asthma). The well designed protocol and case report forms were submitted in the Institutional Ethics committee, NIS for conducting clinical studies and approval was got from the IEC. The IEC approval Number is NIS/IEC/11/02/02.The dully filled Form B (Application for permission for Animal Experiments) was submitted in the Institutional Animal Ethics Committee, NIS and approval was got from the IAEC for conducting pre clinical studies in the Animal model. The IAEC Approval number is NIS/04/2011/11. The clinical trial was registered in the clinical trial Registry of India and the Registration Number is CTRI/2013/12/004253.The clinical trial was also registered in International Clinical Trials Registry Platform and the ID is NIS/PPHD/11/0104. The raw drugs were purchased from the Indian Medical practitioner’s co- operative pharmacy and stores Ltd., X-185 (IMCOPS), Thiruvanmiyur, Chennai. The fresh herbs were collected from the herbal Garden, NIS, Chennai. All the herbal drugs were authenticated by Assistant professor of Botany, National Institute of siddha, Chennai (voucher No. NIS/NB 69/2012) and deposited in the Medical Botany Laboratory NIS, Chennai.The trial drug was prepared in the Gunapadam lab of National Institute of siddha as per the Method of Preparation mentioned in the siddha sastric text and standard operating procedure mentioned in the protocol.The Medicine was then subjected to pre clinical toxicity studies (Acute and sub chronic toxicity studies) as per who Guidelines 1993 in Animal Laboratory National Institute of Siddha to evaluate the safety of the trial drug. The qualitative (preliminary phyto chemical analysis) and quantitative (physio chemical analysis ), TLC and HPTLC finger print profile were done at the Biochemistry laboratory of National Institute of siddha, Siddha Central Research Institute Arumbakkam, Chennai and Captain srinivasa Murti Drug research Institute of Ayurveda and siddha Drug Development, Arumbakkam, Chennai respectively. The Gas Chromatography - Mass Spectrometry (GC-MS) analysis was done at Sophisticated Analytical Instrument facility, Indian Institute of Technology, Chennai to identity the bio active Components of trial drug. Heavy metal analysis, Microbial load and aflatoxin content of trial drug were performed for drug standardization in sargum laboratory which is an AYUSH approved lab for drug analysis. Pilot study was done in 5 OPD cases before starting the main study. 191 cases were screened in the OPD of maruthuvam, NIS by using screening and selection proforma and 138 cases were recruited for the clinical trial as per the inclusion and exclusion criteria. Clinical diagnosis was made by siddha and Modern Methodology. The Informed consent was obtained from all the cases before starting the treatment. Complete clinical history, complaints and duration, examination findings were recorded in the History Proforma and clinical assessment form. Blood and urine investigations, x-ray, ECG and sputum test were taken in NIS and the results were recorded in the Laboratory parameters –chart. The serum IgE level and spirometry test were taken before and after treatment in NABL certified Laboratory. The patients are advised to record their peak expiratory flow rate in morning and evening before taking the trial drug in the peak expiratory flow rate monitoring form. Clinical assessment was done daily in IPD cases, once in 7 days for 30 days in OPD cases and symptoms were recorded in clinical assessment form. Asthma control questionnaire was filled before and after treatment to observe the score changes. Out of 138 cases 123 cases were treated in OPD, 2 cases were in IPD. 13 cases were with drawn during the treatment period. The trial drug Adathodai chooranam was given in the dose of 1.5 gram, twice a day for 30 days. Patients were advised to take the trial drug with cow’s milk. During the treatment period patients were advised to take the diet as per the Dietary advice form.After the treatment period all the 125 cases were followed in OPD without treatment upto 3 months to monitor the recurrence of symptoms. Paired t test was followed to find the significance of treatment using before and after the data on haematological parameters, blood biochemistry, peak expiratory flow rate and spirometry results.The significance probability 0.05(p<0.05) was used to find the treatment difference. Statistical analysis was done by using independent“t” tests for comparison of pulmonary function parameters. CONCLUSION: The quality of the drug is better if the acid insoluble ash value is low which 2.5% is for Aadhathodai Chooranam. In phyto chemical analysis Alkaloids, Flavonoids, Glycosides, Terpenes, Saponins, Aminoacids, Phenols, Tannins, Quinones, Lignans, Steroids, Chloride, Phosphate, Ammonium iron were detected. The Phytochemical analysis results correlate with the literature survey of all the ingredients of Aadhathodai Chooranam which given additional supports to its usage in clinical trial of Bronchial Asthma with potent antioxidant, antiinflammatory, antihistaminic, antispasmodic, immnuomodulator, bronchodilator action. Heavy metal analysis, Microbial load and Aflatoxin content of Aadhathodai Chooranam revealed that the Aadhathodai Chooranam was below the WHO/FDA permissible limits and safe for consumption. HPTLC finger print of Aadhothodai Chooranam could serve as a marker and which is responsible for expression of its Biological and clinical actions. The bioactive compounds identified by GC-MS in the trial drug Adathodai Chooranam possess antioxidant, anti microbial, anti inflammatory and medicinally valuable. In acute and long term toxicity studies, mortality or signs of toxicity were not observed because of administration of Adathodai Chooranam. The single oral dose of 2.6 gm/kg body weight was considered as non toxic drug in acute toxicity study. Long term toxicity study showed that the test drug adathodai chooranam is well tolerated at therapeutic dose level (270 mg/kg body weight and it is proved that the trial drug Adathodai Chooranam is safe as per mentioned in the siddha literature (1.5 g for human adult). During the treatment period the trial drug did not produce any adverse drug reactions in all 125 cases. Clinically among 125 cases 110 cases (88%) showed good response. 5 (4%) cases showed moderate response. 10 cases (8%) showed poor response. By PEFR measurement, Among 125 cases, 106 cases (84.8%) showed good response. 7 cases (5.6%) showed moderate response. 12 cases (9.6%) showed poor response. There were significant decrease in symptoms score before and after treatment and the P –value is <.00001. The siddha parameters like eight diagnostic methods, seven physical constituents, three humors and Neikuri showed improvement to the trial drug during the treatment . There were significant reduction in scores for Absolute Eosinophil count before and after treatment p=<0.499.There were significant reduction in scores for Serum IgE level before and after treatment p=<0.045. There were significant increase in scores for Peak expiratory flow rate (morning) of first week and fourth week of treatment and the P –value is <.00001. There were significant increase in scores for Peak expiratory flow rate (evening) of first week and fourth week of treatment and the P –value is <.00001. After treatment the percentage predicted values of FEVI (L) was increased in spirometry and it was statistically significant p < .05. All the results of clinical study showed that the trial drug is very effective in lowering symptoms of Asthma,reducing Absolute eosinophil count and serum IgE level, improving lung function in new Asthmatic patients (2 year duration) within the treatment period of 30 days. The drug also reduces the recurrent of episode of Asthma symptoms. The ingredients of Adhathodai chooranam possess anti inflammatory, antihistaminic, antiasthmatic, antispasmodic, antimicrobial, expectorant, antitussive, bronchodilator, immunomodulator and antioxidant activities. These properties play a vital role in the treatment of Bronchial Asthma. Hence, it could be concluded that the Adhathodai chooranam is one of the very effective drug for Asthmatic patients. Additionally all the ingredients of Adathodai chooranam possess hot potency and pungent taste.These properties neutralize the kaba humour and reduce the signs and symptoms of Iya EraippuNoi in Siddha system of medicine.