Pharmaceutical, physico-chemical and clinical study on

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Indian Journal of Traditional Knowledge Vol. 3(3), July 2004, pp. 240-246 Pharmaceutical, physico-chemical and clinical study on "Shuddha Manahshila" with special reference to Kasa Roga Atul Kumar TKDL, National Institute of Science Communication and Information Resources, CSIR, New Delhi 110012 E-mail: atulkumar@niscair.res.in;akumar51@rediffmail.com Received 16 January 2004; revised 24 March 2004 Manahshila (Realgar; Arsenic disulphide- AS 2 S 2 ), a bright red-orange coloured mineral, is a compound of arsenic and sulphur in 2:2 ratio, which has been described under Up rasa Varga in Rasa Shastra of Ayurveda. It is found in ore form in nature and can also be made artificially. Manahshila is one of the mineral drugs that has history of usage as old as Vedic period. In Rigveda, its usage has been mentioned for environmental purification; whereas, in Athrvaveda and Purana Granthas, its externo-internal usage is mentioned. Manahshila can therapeutically be used only after Shodhana (purification & detoxification). In the present study, the drug was prepared by processing (Bhavita) from approved are of Manahshila with Adraka Svarasa (ginger juice) for 7 days to make the drug more potent for Kasa Raga (cough/bronchitis). The physico-chemical parameters of the prepared drug were also established for the first time by comparing them with the crude drug, which was novel from pharmaceutical point of view. The clinical study of the drug was performed in 25 patients, at a dose of 10-25 mg, three times a day, for one month, with the adjuvant of Madhu (honey). The drug gave good results, particularly in Vataja Kasa (eosinophilia). Keywords: Ayurvedic drugs, Shuddha Manahshila, Standardization, Kasa raga, Cough, Bronchitis. IPC Int Cr.7; A61K 33/36; A61K 33/04; A61K 35/78; A61K 35/12; A61P 11100; A61P 11114; A61P 11108; A61P ll/06; A61P 29/00;A61P 37/08. Manahshila, also nown as Mainsil, Warangana, Jharanikha surkha, Realgar or Red orpiment, is a deep red, lustrous monoclinic crystalline solid. On rubbing or crushing, it changes into a red-orange coloured fine powder. Manahshila (Arsenic disulphide, As 2 S 2 ), occurs in nature as a mineral and can also be prepared artificially by fusing 49 parts Shuddha MaZZa (purified arsenic) and 16 parts Shuddha Gandhaka (purified sulphur) by processing in a Damaru Yantra (specific instrumerit)", In Rasa Shastra, Manahshila has been described under Up rasa Varga. In Charaka', Sushruta 3 and Vagabattd', it has been described under Parthiva (Bhauma) Dravya Varga; while Sharangadhara' placed it under Upadhatu and Uparasa Varga. Manahsila is one of the

ATULKUMAR: "MANAHSHILA" AND KASA ROGA 241 mineral drugs that has been known to mankind since Vedic period, where its psychological and therapeutic uses were well known. In Rigveda', it has been described as Rakshoghna (disinfectantlbiocidal) drug in physical and mental diseases, where it was used for purification of environment. In Yajurveda and Atharvaveda'; its usage has been mentioned in Agni Vayu Havana Chikitsa, Bhutonmada Chikitsa (treatment of idiopathic psychotic syndrome) and Karmaja Vyadhi Nirodha. In Boddha Sahitya, Vinaya Pitaka, it has been mentioned as Anjana (ophthalmic medication) and Dhruma Varti (medicated smoke); in Agni Purana as Kusthaghna Lepa (anti dermal-diseases/ anti-leprotic paste for local application/ointment); and in Kautilya Arthashastra as Agni Churna for fireworks. In Samhitas, viz. Charakai, Sushruta', Yagbhauo", Harita, Bhela and Kashyapa', its externo-internal usages were mentioned in various diseases, such as Hikka (hiccough), Svasa (dyspnoea), Kasa (cough/bronchitis), Chardi (emesis), Kustha (leprosy and other dermatoses) etc. In Rasa Shastra treatises, it was used in the preparations of Dhruma Varti (medicated smoke), Ghrta (medicated clarified butter/fat based formulations), Taila (medicated oil), Lepa (paste for local application/ointment), Curna Nasya (powdered nasal insufflation), Anjana (ophthalmic medication) and in various Rasa Yoga (organo-mineral/mineral preparation). It has also been used for Rasa Karma (processing of organomineral/mineral preparation) and Dhatu Ranjana (colouring agent for metals) in Rasa Shastra 9,I,IO,ll. Manahshila of three varieties has been described in most of the Rasa Shastra treaties, viz. Shyamangi, Kanaviraka and Khandakhya', However, the Khandakhya variety of Manahshila is widely accepted for therapeutic usage and also for Satva Patana (preparation of metallic extract of mineral ore). Manahshila (Realgar) is used only in Shuddha (purified & detoxified) state for the therapeutic purposes as internal medicine. With reference to the treatment of Svasa and Kasa use of drug Shuddha Manahshila has been described in various Rasa Yoga preparations, such as Rajamriganka Rasa, Trailokyachintamani Rasa, Shilasindura, Samirapannaga Rasa and Shvasakuthara Rasa, Moreover, there are references for the use of Manahshila in Kasa Roga but it has not been used so far independently as a single drug. Therefore, a study was undertaken to use Shuddha Manahshila as single drug for the treatment of Kasa Roga. Shodhana of Manahshila is usually carried out by trituration with Ardraka (Zingiber officinale Rosc.) Svarasa, Bijaura Nimbu (Citrus medica Linn.) Svarasa, Agstya(Sesbania grandiflora Poir.) Svarasa, Jayanti (Sesbania sesban Merr.) Svarasa, Bhrngaraja (Ecipta alba Hassk.) Svarasa and Lime water etc. In the present study Ardraka Svarasa was taken because Ardraka itself is used in the treatment of Kasa Roga and a number of references are available for shodhana of Manahshila with Ardraka Svarasa in Rasa Shastra treatises 9,I,IO,II. In the present study Shuddha Manahshila was

242 INDIAN J TRADITIONAL KNOWLEDGE, VOL 3, No. 3, JULY 2004 standardized and evaluated for its physico-chemical parameters, along with its clinical study in patients of Kasa Roga. Methodology Pharmaceutical Study The drug was prepared by taking Khandakhya variety of Manahshila (400 g). It was processed (triturated) 7 times with Ardraka Svarasa (ginger juice) for 7 days 1. At the end of processing, an orange coloured, smooth, heavy, powder, the Shuddha Manahshila (pure realgar) was obtained. It was noted that the weight of Shuddha Manahshila was increased by 27.5% (110 grammes) after the completion of Shodhana (purification & detoxification)!', as shown in Table l. Physico-Chemical Analysis Many physical and chemical changes occur during the processes of making the drug Shuddha Manahshila. Various steps involved in drug standardization have been applied to Suddha Manahsila, as shown in Figure 1. Standardization of "Shuddha Manahshila" A very fine orange powder (s,.huddha Manahshila) obtained after Shodhana of Manahshila, as mentioned in The Ayurvedic Formulary of India l2, was used for physico-chemical study. The physico-chemical parameters 13 of the drug, Shuddha Manahshila are as follows: Physical parameters: Colour Odour Taste Touch : Orange : Pleasant pungent : Agreeable bitter : Heavy & smooth powder Chemical parameters: Qualitative analysis Identification: Yielded the reaction characteristics of Arsenic (As) & Sulphur (S)14.15. Quantitative analysis Loss on drying at 1l0"C : 0.5325%, w/w Loss on ignition at 450- : 95.0686%, w/w 550 C Ash value : 4.9544 %, w/w Water insoluble ash : 4.1978 %, w/w Acid insoluble ash : 0.5008%, w/w Special quantitative analysis Elemental Therapeutic Dose study indication : The quantitative element study was carried out through Atomic absorption spectroscopy and Inductive couple plasma (Instrumental element test)"; as shown in Table 2. : Kasa (cough! bronchitis) : 10-25 mg Table 1 - Weight differentiations of pharmaceutical processing of Manahsila Weight of Weight Of Increase Percentage of weight Manahshila Manahshila in weight of prepared increase in prepared crude drug prepared drug drug drug (before processing) -(after processing) 400 Grarnmes 510 Gramrnes 110 Gramrnes 27.5%

ATULKUMAR: "MANAHSHILA" AND KASA ROGA 243 Figure 1-[A] Manahshila or Realgar (Crude drug) [B] Shodhana of Manahshila (Processing or triturating of drug) [C] Shuddha Manahshila (Prepared drug)

244 INDIAN J TRADITIONAL KNOWLEDGE, VOL 3, No. 3, JULY 2004 Table 2 - Percentage of element analysis in sample "0" & "A" of Manahshila Analyzed Sample "0" Sample "A" elements Manahsila Suddha (crude drug) Manahsila (prepared drug) Arsenic (As) 7.2989 % 7.0149 % Sulphur (S) 17.000 % 12.9000% It is clear from the above physicochemical study that many physical and chemical changes occurred in the drug after it was processed (triturated) with Ardraka Svarasa. The drug became detoxified and made the drug more potent. Moreover, the inorganic state of drug changed into organic state. Clinical Study The clinical study of Shuddha Manahshila was performed on 25 patients, at O.P.D. & Indoor Department of Kaya Chikitsa, Rishikul Government State Ayurvedic College & Hospital, Hardwar, Uttaranchal. The study was carried out in a particular "Proforma", in which the selection of registered patients of Kasa Raga was done according to parameters of their definite symptoms of Kasa, pathological tests and other diagnostic examinations. The therapeutic effect of the drug was observed after 4 weeks of treatment. The effect of the drug was assessed in weekly follow-ups for 4 weeks, using the above-mentioned parameters. After follow-ups or cure of the disease, whichever is earlier, data were collected and analyzed statistically. The drug: Shuddha Manahshila 9 1 Dose of drug: For adult - 25 mg, three times a day, with the adjuvant of honey. For child - 10 mg, three times a day, with the adjuvant of honey. The clinical effects of Shuddha Manahshila on the patients of Kasa Raga were observed for 4 weeks. Results During the treatment of Kasa Raga, the patients observed for the complications I 0 of Manhashila, such as Vamana (vomiting), Trisna (polydipsia/excessive thirst), Mandagni (dyspepsia/loss of appetite), Malabaddhata (constipation) and Mutra Vikara(diseases of the urinary system) etc., showed no complications. The clinical effects of Shuddha Manahshila on the patients of Kasa Raga Table 3--Result of clinical study of Shuddha Manahshila on patients of Kasa Roga S.N. Results Male No. of patients Female Total no. of patients Percentage I. Cured 10 9 19 76% 2. Improved 3 4 16% 3. Not Improved 2 8% Total 14 11 25 100%

ATULKUMAR: "MANAHSHILA" AND KASA ROGA 245 were observed on the basis of progress of their symptoms of Kasa and pathological tests, e.g. TLC, DLC, Hb% and E.S.R. parameters 17, every week for 4 weeks of drug treatment. The prognosis was observed on the basis of subjective & objective relief. 76% patients of Kasa Raga were cured and 16 % improved with the treatment of Shuddha Manahshila; however, 8% did not show any change in their conditions as shown in Table 3. Differential leucocytes counts (DLC) were carried out as a part of clinical study. In Ayurveda, Vatika Kasa is correlated with eosinophilic cough and according to modern medicine, eosinophills count usually rises during respiratory ailments". The effect of the drug was studied with respect to eosinophills percentage change in one-week interval. Out of 25 patents of Kasa Raga, eosinophills percentage reduced significantally in 20 patients, no significant change was observed in 3 patients and data could not be collected from 2 patients, as they did not continue the treatment. Shuddha Manahshila gave a good prognosis in the patients of Vatika Kasa (coughlbronchitis with Vata predominance-eosinophilia) in comparisons to other types of Kasa, which were observed on the basis of subjective and objective improvement. Conclusion During the present clinical study of Shuddha Manahshila on the patients of Kasa Raga, no side effect of the drug was noticed. Shuddha Manahshila, when given to patients of Kasa Raga at the dose of 10-25 mg, three times a day for 4 weeks, with the adjuvant of honey, gave good result particularly in Vatika Kasa (eosinophilia). Shuddha Manahshila, if used in appropriate dose on the patients of Kasa Raga, has a potential for becoming the drug of choice. References 1 Sadananda Sharma, Rasatarangini, edited by Dharmanand Shastri, l l th Ed., (Motilal Banarasi Das, Delhi), 1979. 2 Agnivesa, Charaka Samhita, Commentary by Kashinath Shastri, 1st Ed., (Chaukhamba Sanskrit Academy, Varanasi), 1991. 3 Sushruta, Sushruta Samhita, Commentary by Ambika Dutta Shastri, l st Ed., (Chaukhamba Sanskrit Sansthan, Varanasi), 1987. 4 Vagbhata, Astanga hrdaya, edited by Bhisagacarya Hari Shastri Paradakara Vaidya, 8th Ed., (Chaukhamba Orientalia, Varanasi), 1998. 5 Sharangdhracarya, Sarangadhara Samhita, edited by Smt Shailja Srivastava, 2nd Ed., (Chaukhamba Orientalia, Varanasi), 1998. 6 Rigveda, Commentary by Vishva Bandhu, 1st Ed., (Vishveshvaranand Vedic Research Institute, Hoshiarpur), 1965. 7 Atharvaveda, Commentary by Vishva Bandhu, Ist Ed., (Vishveshvaranand Vedic Research Institute, Hoshiarpur), 1960. 8 Vrddhajivaka, Kashyapa Samhita or Vrddhajivakiya Tantra, edited by P V Tiwari, Ist Ed., (Chaukhamba Visvabharti, Varanasi), 1996. 9 Vagbhattacharya, Rasaratnasamuchchayah, edited by Indradev Tripathi, 2nd Ed., (Chaukhamba Sanskrit Sansthana, Varanasi), to 2000. Pt. Datta Ram Chaube, Brhadrasarajasundara, 3rd Ed., (Chaukharnba Orientalia, Varanasi), 2000. II Siddhinandan Mishra, Ayurvediya Rasa Shastra, l lth Ed., (Chaukharnba Orientalia, Varanasi),200l. 12 Ayurvedic Formulary of India Part II, Ist English Ed., (Govt of India, Ministry of Health & Family Welfare, New Delhi), 2000.

246 INDIAN J TRADITIONAL KNOWLEDGE, VOL 3, No. 3, JULY 2004 13 Pharmacopoeial Standards for Ayurvedic Formulations, 1st Ed., (Govt of India, Ministry of Health & Family Welfare, New Delhi), Reprint 1997. 14 Wiley's Textbook of Inorganic Chemistry, 6th Ed., (John Wiley & Sons), 1985. 15 Vogel's Textbook of Quantitative Chemical Analysis, J. Bassett, J. Mendham, G. H. Jeffery, R. C. Denney (Contributors), 5th Ed., (Addison-Wesley Pub Co.), 1989. 16 Burton F. Pease's Basic Instrumental Analysis, 1st Ed., (Krieger Publishing Company), 1980. 17 Devidson's Principles and Practice of Medicine Edited by Christopher Haslett, Edwin R.Chilvers, John A.A.Hunter, Nicholas A. Boon, 18th Ed., (Churchill Livingstone), 1999. 18 Hutchisons Clinical Methods by Swash Michael; Hutchison, Robert, 20th Ed., (W.B. Saunders Company, London), 1995.