1. PHYSICOCHEMICALANALYSISOFSAMANYA&VISHESHASHODITA TAMRAANDTOXICOLOGICALSTUDYOFTAMRABHASMA By DR. SHAMBHULING. V. TEGGI DISSERTATION SUBMITTED TO THE RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE IN PARTIAL FULFILLMENTS FOR THE DEGREE OF AYURVEDA VACHASPATHI M.D. In RASASHASTRA UNDER THE GUIDANCE UNDER THE CO-GUIDANCE DR.DILIPKUMAR.B. DR. GIRISH.N.DANAPPAGOUDAR M.D.(R.S) M.D(R.S) Asst.Professor Lecturer. POST GRADUATE DEPARTMENT OF RASASHASTRA D.G.M. AYURVEDIC MEDICAL COLLEGE. GADAG 582103 2006 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

2. DECLARATIONI here by declare that this dissertation entitled PHYSICO-CHEMICAL ANALYSIS OFSAMANYA AND VISHESHA SHODHITA TAMRA AND TOXICOLOGICAL STUDYOF TAMRA BHASMA is a bonafide and genuine research work carried out by meunder the guidance of Dr.Dilipkumar.B. Asst.Professor. Department of Rasashatra,Post Graduate cum Research Center, D. G. M Ayurvedic Medical College, Gadag 582103Date: Dr.Shambhuling.V.Teggiplace: Gadag.

3. ENDORSMENT BY THE HOD, PRINCIPAL/HEAD OF THEDepartment of Post Graduate INSTITUTATION Post Graduate cum Research Center,Studies in RASASHASTRA D.G.M.Ayurvedic Medical College Gadag 582103 J.S.V.V. SAMITES ENDORSEMENT I here by declare that this dissertation entitled PHYSICO-CHEMICAL ANALYSIS OF SAMANYA AND VISHESHA SHODHITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA is a bonafide and genuine research work done by Dr.Shambhuling.V.Teggi under the guidance of Dr.Dilipkumar.B. Asst.Professor. Department of Rasashastra Post Graduate Studies & Dr.Girish.N.Danappagoudar Lecturer, Department of Rasashastra, Post Graduate Studies in D.G.M.Ayurvedic Medical College, Gadag. Dr.M.C.PATIL.M.D. (AYU) Dr.G.B.PATIL. Professor. & HOD. PRINCIPAL Post Graduate Department of RASASHASTRA

4. Department of Post graduate Post Graduate cum Research Center, Studies in RASASHASTRA D.G.M.Ayurvedic Medical College Gadag 582103 J.S.V.V. SAMITES CERTIFICATE I here by declare that this dissertation entitled PHYSICO-CHEMICAL ANALYSIS OF SAMANYA AND VISHESHA SHODHITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA is a bonafide and genuine research work done by Dr.Shambhuling.V.Teggi in partial fulfillment of the requirement for the degree of Ayurveda Vachaspati (M.D) in RASASHASTRA of Rajiv Gandhi University of Health sciences, Bangalore, Karnataka. Guide Date: Dr.Dilipkumar.B. Place: Gadag. M.D.(R.S). Asst.Professor. Department Rasashatra Post Graduate cum Research Center D.G.M.A.M.C Gadag 582103

5. Department of Post graduate D.G.M.Ayurvedic Medical College &Studies in RASASHASTRA Post Graduate cum Research Center Gadag 582103 Dist: Gadag J.S.V.V. SAMITES CERTIFICATEI here by declare that this dissertation entitled PHYSICO-CHEMICALANALYSIS OF SAMANYA AND VISHESHA SHODHITA TAMRA ANDTOXICOLOGICAL STUDY OF TAMRA BHASMA is a bonafide and genuineresearch work done by Dr.Shambhuling.V.Teggi in partial fulfillment of therequirement for the degree of Ayurveda Vachaspati (M.D) in Rasashastra ofRajeev Gandhi University of Health sciences, Bangalore, Karnataka. Co-GuideDate: Dr.Girish.N.DanappagoudarPlace: Gadag. M.D.(R,S.) Lecturer. Department Rasashatra Post Graduate cum Research Center D.G.M.A.M.C Gadag 582103

6. COPYRIGHT Declaration by the candidate I here by declare that the Rajeev Gandhi University of Health Sciences,Karnataka shall have the rights to preserve, use and disseminate this dissertation inprint or electronic format for academic / research purpose.Date: Dr.Shambhuling.V.Teggi.Place: Gadag Rajiv Gandhi University of Health Sciences, Karnataka

7. ACKNOWLEDGEMENT I am extremely grateful to my respected and honorable principalDr. G.B.Patil.for providing all the facilities and encouragement to make this studysuccess. It is great pleasure for me to express my gratitude with profound respect to myrevered Guide Dr. Dilpkumar B.M.D. (Ayu) Assit. Professor. and Dr. M.C. Patil. M.D.(Ayu) H.O.D, Department of P.G. Studies in Rasashastra. for his indefatigable andindefeasible guidance, his constant inspiration and encouragement gave meconsiderable impetus and co-operation through out my study. I am grateful to my co-guide Dr. Girish. Danappagoudar. MD (Ayu) Lecturer,Dept. of Rasashastra. for his continuous Guidelines and valuable suggestionsthroughout the studies. I am highly grateful to Dr. Jagadish Matti. MD (Ayu) Dept. of Rasashastra.For his moral encouragement valuable suggestions and help. I express my sincere gratitude to Dr. V. Varadacharyulu M.D (Ayu), Dr.Mulgund M.D (Ayu), Dr. K. S. R. Prasad M.D (Ayu), Dr. Kuber Sankh M.D(Ayu), Dr.Gacchinamath and other PG staff for their constant encouragement. I sincerely thanks to Dr. Jaggal. Dr.S.S.Gangoor. Dr.V.M.Sabarada Dr.A.I.Akkifor his valuable advises throughout my dissertation work. I express heartful thanks to my wife Dr.Tanuja and daughter Anusha and MasterAkshaya for her inspiration and encouragement. i

8. I wish to express thanks to my colleagues Dr, Lingareddi Dr. Ananda, Dr.Sharanu Dr. Suvarna Dr.Anitha Dr. V.S.H.iremata Dr.Koteshwar Dr. PradeepAgnihotri, Dr.Basavaraj. Ganti, Dr.M.V.Sobagin.,Dr. Saswihalli, Dr Rudrakshi Dr.Kavitha Dr. Katti and other scholars of my college I am sincerely thanks to Dr. H. R. Chitme, M.Pharm., Ph.D. -Assoc. ProfessorH. S. K. College of Pharmacy Bagalkot Project Director, Mr. G. S. Hiremath, M.PharmPharmacologist, Mr. D. Nandeesh, M.Pharm. Toxicologist. Mrs. Praveena ChillaleM. Sc.- Research Officer, Statistician and H. S. K. College of Pharmacy Bagalkotother staff for their valuable co-operation and suggestions in Toxicological studies. I express my gratitude to Dr. S..A.Kori PROF Dept of Mechanical engineering andRaju Kurahatti ASST PROF. Basaveshwar engineering college Bagalkot and staff for hisvaluable advises in Physical and Chemical study I sincerely thankful to Sri. Nandakumar Statistician for his kind help and co-operation in statistical data analysis. I am ever grateful to those who have helped me directly and indirectly tocomplete this dissertation. Dr.Shambhuling.V.Teggi. ii

9. ABBREVIATIONS1. A.K -Anandakanda2. A.P -Ayurveda Prakasha3. AS -Astanga sangraha4. B.P. Bhavaprakasha5. B.R -Bhaishaja Ratnavali6. C.S -Charaka Samhita7. Dh.NI. -Dhanwantri nighantu8. R.J.N -Rasajalanidhi9. R.K.D. -Rasakamadenu10. R.T. Rasa tarangini11. R.C - Rasendra Chudamani12. R.K. Rasa Ratnakara13. R.S.S - Rasendra sara sangra14. R.H.T. Rasa Hridaya Tantra15. R.Mr. - Rasamrutha.16. R.P.S. -Rasaprakasha sudhakar17. R.R.S. Rasa rathna samuchaya18. R.M. - Rasa manjiri19. S.B.M. Sidda bhaisajya manu20. S.S. -Susrutha sahimtha21. Sa.Ni -Saideva Nigantu22. V.R. Vasarajiyam23. Y.R. -Yoga ratnakar iii

10. ABSTRACTBackground & objective: If Tamra Bhasma is not prepared with a proper shodhana & marana Navishamvishamuchyate tamra vishamuchyate is the classical verdict. This interested us to knowthe exact changes that occur in tamra so that it changes from visha to a celebratedtherapeutic tool.Methods Tamra was subjected to samanya shodhana as described in RRS. After thesamanya shodhana it was subjected to vishesha shodhana. It these two processes whichare attributed to have anti-toxicological activity on tamra. Samanya & vishesha shuddhatamra was taken up for evaluation of physico- chemical analysis.Tamra bhasma was doneas per RRS & was evaluated with siddhi lakshanas described in RRS. The lakshanasevaluated were apunarbhava, waritara, nishchandra, avami, niruttha, rekhapoornata, andnirdhooma & amladravya pareeksha. In addition the bhasma was taken up for a toxicitystudy.Results The tamra when subjected for samanya shodhana was becoming brittler & harderwith each nirvapa. The malleability & ductility of the metal was decreasingprogressively. Tamra had lost its metallic lusture at the end of the process & had ablackish discoloration.The toxicity studies on swiss albino mice showed no toxicity at 3.0mg/kg dosage, whichtranslates in 57.26 - 286.53 mg for an adult dosage. The Tamra Bhasma dosage being 1/4to1 ratti i.e. (30mg-120 mg). iv

11. Interpretation & conclusion: The shodhana (Samanya & vishesha) makes the tamra hard & brittle so that thebhasma process becomes easier.The tamra bhasma thus prepared is safe even at 5 timesthe highest therapeutic dosage. Improperly prepared tamra bhasma produces all the classical visha lakshanasdescribed under tamra visha lakshanasKey words: Tamrabhasma, Samanya shodhana, visesha shodhana, marana. v

12. CONTENTS Chapter Page No.1. Introduction 1-052. Objectives 63. Review of Literature 7-704. Materials and Methods 71-1375. Results 138-1486. Discussion 149-1567. Conclusion 1578. Summary 158-1599. References i-xv10. Appendix vi

13. LIST OF TABLES Sl Tables Page N0 No 01 Synonyms of tamra 28 02 Rasa of tamra 32 03 Guna of tamra 33 04 Virya of tamra 33 05 Vipaka of tamra 33 06 Karma of tamra 34 07 Asudda tamra dosha 36 08 Tamra shodhana 39 09 Various drugs used in Tamra shodhana 41 10 Classification of Hingula according to ancient period 52 11 Rasa of Hingula 54 12 Synonyms of Parada 57 13 Vernacular names of Parada 58 14 Synonyms of Gandhaka 61 15 Gandhaka shodhana 62 16 Dalana,Bhavana, and Swedana of Gandhaka 62 17 Properties of shudda Gandhaka 63 18 Hingula shodhana 75 19 Gandhaka shodhana 80 20 Toxic study of schedule 112 21 Dosage schedule 124 22 Body weight changes and Pre-terminal deaths 125 23 Organ to body weight ratio(g) at 300mg/kg PO 126 24 Histopathological Observations 126 25 Toxic sign, Pre-terminal deaths 130 26 After discontinuing treatment ( 30 days expt ) 131LIST OF PHOTOGRAPHS: Sl. No Photographs Page No 1 Toxic study of tamra bhasma 129 2 Toxic study of tamra bhasma 129 vii

14. INTRODUCTION INTRODUCTION Science is not a sudden invention. It is a gradual evolution. Science is theintellectual process for using all of the mental and physical resources available inorder to better understand. Ayurveda as a science is not an exception for it. It is not justa curative medicine, but also it teaches the way to live long healthy and happy life. Ayurveda is one of the systems of medicine in the world. Among so manysystems of medicine it has its own identities. Because, it deals with health as well asdisease. The aims of Ayurveda are preserving and promoting health as well as preventingand curing diseases. Ayurveda defines swastha as one whose physical, spiritual, socialand environmental aspects are in a good harmony. Ayurveda has taken maximum care to consider even routine events of the dailylife in view of their vital role in promoting health and preventing disease. Almost everysource of life and matter surrounding human being has been in use for treating thedisease. The scientific approach to understand anything involves observation,measurement of entities that can be quantitated the accumulation of data, andanalysis of the findings distinguished from an intuitive approach. Also science isthe light an intuitive approach. Also science is the light thrown an silent factswhich are hidden in the word-womb. The imperishable fundamentals of Ayurveda, which were laid down by thegreat sages of the olden days are still applicable because of their scientific eternalbackground. Such fundamentals must be subjected to scientific research not onlyto prove its certainly but also to add something new to the existing knowledge. 1PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

15. INTRODUCTION Rasa Shastras deals with various pharmaceutical process of Shodhana, Maranaand other different formulatory methods viz Parpati, Potali, Kupipakva rasayana. Out ofthese Bhasmas are more commonly used in practised for treatment purpose. Bhasmas areunique preparations, which are prepared by Puta system, which is categorically, indicatedifferent kinds of putas (incineration processes) for different kinds of metals and mineralsaccording to their physical and chemical characters. By the process of Marana by usingputa paka metals and minerals get converted into the form of Bhasma (organometalliccompounds) becomes micro fine form. A careful survey of the original texts on Rasasastra shows that the subjectcovers the entire field of inorganic pharmaceutical preparations like metallic, non-metallic compound of Ayurvedic materia medica.On internal administration ofmetals and minerals i.e. Rasausadhis, in unprocessed or misprocessed form, theyare very toxic but when scientifically Shodhana and Marana of these substancesare done with some special processes, they became non-toxic or least toxic withlow untoward effects and can be used therapeutically with high gratitude ofefficacy,.Alpasyapi Maharthatwam Prabhutasyalpa Karmatam Kuryat SamyogaVishlesha Kalasamskar Yukti Bhihi1 This means that by administering a little quantity of medicine should showmore results. This property of the medicine will be achieved when it goes throughparticular samskaras. Rasa Shastra which developed as a fragrance of Ayurveda in peak at the medieval 2PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

16. INTRODUCTION period highlights Tamra in duel forms i.e. Dhatu Vada and Deha Vada even, later duringthe budding of Chikista Vada itself Tamra was signified and to make it a homologous tothe body the various methods were attributed by various Acharyas and almost all of themhave praised the processing of Tamra with Parada for the desired action in the humanbody Healthy or Diseased. Information available on Tamra from coinage period to 20thcentury self indicate its importance through-out, past, present and future. Our present dilemma is that a large quantity of continuously expanding andchanging informations, gradual over powering of our clinical hands and works by theimplant manufacturing houses and highly technical and costly equipments are smartlyavailable, yet more and faster information services have not been significantly translatedinto better care of patients. Even with appropriate information an experienced clinicianwill be reluctant to change his mind, management protocols & treatment behavior, untilthe new principles and techniques have established their credentials harmlessly with wideacceptance. Research is a scientific and unbiased study, investigation or experimentation inorder to establish facts and analyse their significance. Research is done for establishingnew facts, reconfirming old facts or correcting and modifying them. Research is to findout truth through new light on old facts, concepts and practices. There is sample proofthat appropriate research was done even at the time, when original Ayurvediccompendias were written, rightly highlighted by Charaka as - Parikshya Kareno hiKushala Bhavanti.Classics pinpoint the importance attached to Research in Ayurveda.Rasashasta is a very prominent example of research in Ayurveda. Research work is theonly means for the development of any branch of science. Rasashastra is not an 3PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

17. INTRODUCTION exemption to it. Moreover, Rasashastra having an antique background has lost itscontinuity at several places due to several reasons. The discontinuity leads tomisconception regarding earlier procedures and principles. Later, scholars andcommentators tried to fulfill the lacunae to some extent; still the present generation is indilemma regarding the precious concepts explained in Rasashastra due to over shadow ofmodern science. Research work is only away to procure the necessary knowledge to re-link thisdiscontinuity. Bhasmas are the most potent pharmaceutical preparation of Rasashastra.All the metals and minerals are usually used after MARANA. The classical texts ofRasashastra have given several methods of incineration of the substances like Mercury,Orpiment etc. These substances which are unstable in the lowest heat have createddifferent opinions among the some, about getting their Bhasmas but there are plenty ofevidences for preparation of their Bhasmas. Some what similar explanation is seen in Charaka Vimana 8th chapterwhere a hypothesis laid out by a Scholar is explained as Siddhanta the analysis of thesame in experimental, clinical like various angles as Bahuvidha Pariksha then prove thehypothesis with valid reasons as Hetubhihi Sadayitwa by which we can establish theconclusion as Sthapayitwa Nirnaya. In a nut shell Hypothesis examined by properlyplanned experiments and critically discussed data and arrived at reasonable conclusiononly as command the attention of the seekers of truth. By this way only, we can re-establish our faith in old truths mentioned in our Shastras and also expand the area of ourknowledge, develop and add to our present fund of knowledge and advance in newintruded directions. 4PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

18. INTRODUCTION With this view of signifying Tamra, and there analytical and toxical study viewTamra Bhasma was selected for the study and as a part of Bio-standardization of the testdrug, 5PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

19. OBJECTIVES Aims and Objectives of the Study 1. Samanya Shodhana of Tamra. 2. Vishesha Shodhana of Tamra. 3. Preparation of Tamra Bhasma 4. Physicochemical analysis of Ashodhita Tamra. 5. Physicochemical analysis of Samanya Shodhana of Tamra. 6. Physicochemical analysis of Vishesha Shodhana of Tamra. 7. Toxicological study of Tamra Bhasma 6PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

20. REWIEWOFLITERATURE REWIEW OF LITERATURE - DRUG RIVIEW 1. Histological review 2. Synonyms 3. Name in different language chemical symbol 4. Types 5. Grahya tamra laxana 6. Availability 7. Agrahya tamra laxana 8. Pharmacodynamics i. Guna ii. Rasa iii. Virya iv. Vipaka v. Karma 9. Uses 10. Vishalaxana of Ashodhita tamra bhasma 11. Samanya & vishesha shodhana method 12. Marana 13. Amrutikarana 7PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

21. REWIEWOFLITERATUREHistological review: History makes a young man to be old without either wrinkles or gray hairs;privileging him with the experience of age without either the infirmities orinconveniences these of. - Fuller. The above statement apply defines the need for a through historical review priorto dealing with the subject matter. For convenience, the historical review is done undervarious headings. Tamra is an age old metal of coinage are or also named as copper ageand its presence in all the ages signifies the importance of Tamra.Rigveda: * Tamra is discussed in 5/58/2 where Karkana Dharana is seen. * Also Tamra used as ornaments 5/53/4. * Tarma used as utensils, weapons etc. even.Yajurveda: * Tamra is quite evident in Yajurveda even * Few of commentators on Yajurveda opine Loha as Tamra and Shyama as Ayas because while explaining Rajata, Swarna etc. Loha colour minics as Tamra Varna i.e. Aruna or Babru Varna which are found in Tamra and not in Ayas.Shukla Yajurveda:Few of the commentators like Mahidhara Acharya opine that Sesa of Shukla Yajurvedaas Tamra.Atharvaveda:Here clearly Tamra is explained as one among the 3lakhs i.e. Tamra, Kamsya & Pittalawhich were used for ornaments & also Tamra Suci is mentioned. 1/34/6, 1/34/7, 20/8/31 8PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

22. REWIEWOFLITERATUREBrahmana Grantha: Tamra Mudra was used because Tamra was Mridu and can be mould to any shapeif necessary.Shatapatha and Gopatha Brahmana: * Raktayas i.e. Red coloured metal is explained as Tamra. * Tamra Patra is mentioned.Grihya Sutra: * Tamra as Suryaloha * Tamra for Yantra Nirmana was in practice.Dharma Sutra: * Tamra is considered as Pavitra. * Gautamadi Rishis made a rule for Yajna that the vessels should be of Tamra this is most sacred.Puranas: * In Varahs Purana Tamra Utpatti is explained. * In Devi Bhagavata Common man used Tamra.Smriti Yuga: * In Manu Smriti for measurements like Karsha, Para etc. use of only copper vessels are explained. * Also Tamra Patra cleansing is told by the use of Kshara 5/114Charaka Samhita: * Bahya & Abhyantara Prayoga of Tamra is explained. * For Visha Chikitsa 9PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

23. REWIEWOFLITERATURE * For Hrd Shuddhi after Vamana also various references is explained scattered In Charaka Samhita few of them are Charaka Sutra 1/70, 1/131, 1/132, 5/74.Charaka Sharira 3/16, Charaka Indriya 1/18, Charaka Chikista 1/3/47, 49;1/3/58; 1/4/22; 7/117,118; 17/125; 21/131; 23/267,269; 26/246; 26/254,255. Charaka Siddhi 3/7.Sushruta Samhita: * Rasa, Guna, Virya etc. are explained in Su. Su 46/327, * As Rasanjana to increase Dristi Bala etc. Sh. Su 18/85 also other references of Tamra in Sushruta Samhita are found scattered through out three text of them are: Sushruta Samhita Sushruta Sutra: 38/30; 45/11; 46/361Sushruta Chikista: 12/9; 18/19; 19/20.Sushruta Uttara: 11/5; 12/3; 12/6; 13/7; 12/8; 12/10; 12/11; 12/12; 12/14; 15/11; 17/38; 17/43; 18/7; 18/30, 3; 42/25.Ashtanga Sangraha: * In Sutra 22 Tamra Guna, Virya is explained. * Also scattered information is seen throughout the book.Harita Samhita: * In the form of Shikhi Pichcha and Kamsya even is explained. * Also reference of Tamra is Prathama Sthana 5/38 & 5/41, 42 and in Tritiya Sthana 7/42.Also similarly references in Kashyapa Samhita and Bhava Prakasha also are quite evident.Maurya and Nanda dynasty:Tamra Mudra as Raja Mudra but not in general market, it was only for official use. 10PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

24. REWIEWOFLITERATUREKautilya Arthashastra: * Seven Dhatus are mentioned among that Tamra is one. * Akiradhyaksha (Treasurer) was suppose to protect Tamra along with gold & silver.Jaina Period: * Mining of Tamra is mentioned. * Melting of Tamra was known. * Seraka and Savaraka worked for progress of metals including Tamra.Aryakala: * There were experts in India & people around the world came to India to learn the techniques of mining. Attained metal was examined for purity or else the impure was discarded.Shukranitisara: * Dhatu avshadi methods developed.Bhartrihari Niti Shataka; * Reference of Tamra is seen.Rudra Yamnala TantraIn Sloka 14, 63 and 73. * Dhatu Khanija Marana Prakara * Shulba Jirna Prayoga * Shulbabhra Vidhana etc. explained. But in detail about the types, Shodhana Marana etc. is mentioned in almost all the 11PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

25. REWIEWOFLITERATURE Rasagranthas.Books like Rasarnava, Rasa Hridaya Tantra etc. which areconsidered as the oldest classic in these texts Tamra is used in Dhatu Vidya but oraladministration of Tamra is not very clear, but they have mentioned about the Bhasma inthe text suggests they knew the techniques of Bhasmikarana. Later during 12th century as in Rasendra Chudamani Tamra Bhedha, ShrostaTamra Sakshana, Shodhana Marana is explained. Somanathiya Tamra Bhasma a specialmethod of preparing Tamra Bhasma with parade etc. is explained possibily for the firsttime. Later more details, the use of Tamra is various pharmaceutics etc. is also explainedin later Granthas of 13th on Rasa Prakasha Sudhakara and Rasa Ratna Samuchchaya. InRasendra Chintamani of 14th on of Dundukanatha Tamra Bhasma Guna equating toSwarna is explained also Rajata Tamra Parpati Vidhana and by Tamra Yoga Virya PusthiDipana Deha Dridata, Divya Drishti, Dhirgayu etc. are explained also used in - Shoola,Amlapitta, Swayathu, Yakshma & Kushta Roga with Tamra as medicine is explained thisexplains about the oral administration as advanced in later text is evident. InRasapaddhathi of 16th Century. With devigana Gandhaka and preparing SomanathiyaTamra Bhasma in Bhanda Yatra is explained. In 17th Century. In Ayurveda Prakasha theParadena Marita Tamra Bhasma as Sachandrika Yukta is explained. Also in Rasa KarmaDhanu, Rasa Chudamani and Yoga Ratnakara detailed Tamra Shodhana, Marana etc.mentioned. Yoga Ratnakara Bhasma as Kupipakeva Rasayana in a Kupi over ValukaYantra. Rasa Tarangini, Rasa Yoga Sagara and Bharata Bheshaja Ratnakara of the 20thcentury Tamra in a separate chapter etc. is been explained.By this method of study itsquite evident that initially Tamra was used as Dhatu Vidya then later entered by 12PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

26. REWIEWOFLITERATURERasacharyas is Chikista Kshetra in various compound preparations and as many ofpharmaceutical preparations. Sindhu Pradesha Harappa, Punjab etc. copper items were excavated. Harappa Mohenjodaro as per the available reference it was demolished &reconstruct 3 times hence forth layer by layer foundation is excavated and copper wasfound in the oldest foundation zone itself suggests the availability of copper in earliercivilizations itself. 400yrs before this in Babylonion civilization also in Irau copper instrumentswere found. A China scholar 3081 yr before, Jha a person from Turkistan basically & establishedin West China at this time copper & Kashya were given as gifts. Mishra Pyranids as per written on papyrus in this book its written that kdg of copperon 5000yr ago. Afghanistan, China, Lydia, India Mudra of copper found. Cypriyarm was name of copper. During Rome Kanayasam. Late Rome Cupriyam Later into Cuppram English - Copper During Roman civilization as gold was costly copper was famous. Cupriyam cu = earth, priyam found Copper was found (Priyam) of Bhoomi (Cu). 13PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

27. REWIEWOFLITERATUREHistoric review of copper As medicine in modern view2: The first recorded medical use of copper is found in the Smith Papyrus, one of theoldest books known. The papyrus is an Egyptian medical text, written between 2600 and2200 B.C. which records the use of copper to sterilize chest wounds and to sterilizedrinking water. Other early reports of coppers medicinal use are found in the EbresPapyrus, written around 1500 B.C. The Ebers Papyrus documents medicine practiced inancient Egypt and in other cultures that flourished many centuries earlier. Coppercompounds were recommended for headaches, trembling of the limbs (perhapsreferring to epilepsy or St. Vitus dance) burn wounds, itching and certain growths in theneck, some of which were probably boils. Forms of copper used for the treatment ofdisease ranged from metallic copper carbonate. It could also have been chrysocolla, acopper silicate or even copper chloride, which forms on copper exposed to seawater. Inthe first century A.D., Dioscorides, in his book De Materia Medica described a method of making another green pigment knownas verdigris by exposing metallic copper to the vapors of boiling vinegar. In this process,blue-green copper acetate forms on the copper surface. Verdigris and blue vitriol (coppersulfate) were used, among other things, in remedies for eye ailments such as bloodshoteyes, inflamed or bleary eyes, fat in the eyes (trachoma?). In the Hippocratic Collection (named for, although not entirely written by, theGreek physician Hippocrates, 460 to 380 B.C.), copper is recommended for the treatmentof leg ulcers associated with varicose veins. To prevent infection of fresh wounds, theGreeks sprinkled a dry powder composed of copper oxide and copper sulfate on thewound. Another antiseptic wound treatment at the time was a boiled mixture of honey 14PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

28. REWIEWOFLITERATUREand red copper oxide. The Greeks has easy access to copper since the metal was readilyavailable on the island of Kypros (Cyprus) from which the Latin name for copper,cuprum, is derived. By the time the Roman physician Aulus Corelius Celsus began practicingmedicine, during the reign of Tiberius (14 to 37 A.D.), copper and its derivatives hadbeen firmly established as an important drug in the medical practitioners pharmacopoeia.In Celsus series, De Medicina, books one through and the form of copper most effectivefor each ailment. For the treatment of venereal disease, for example, Celsus prescribed aremedy consisting of pepper, myrrh, saffron, cooked antimony sulfide and copper oxide.These were first pounded together in dry wine and when dry, once again poundedtogether in raisin wine and heated until dry. For a non-healing chronic ulcer treatmentconsisted of copper oxide and other ingredients including enough rose oil to give a softconsistency. Pliny (23 to 79 A.D.) described a number of remedies involving copper. Blackcopper oxide was given with honey to remove intestinal worms. Diluted and injected asdrops into nostrils, it cleared the head and when taken with honey or honey water, itpurged the stomach. It was given for eye roughness eye pain and mistiness, andulceration of the mouth. It was blown into the ears to relieve ear problems. In the New World the Aztecs also copper for medical purpose. Don Francisco deMendoza commissioned two learned Aztec Indian Physicians to record thepharmacological treatments known by the Aztecs at the time of the Conquest. For thetreatment of Faucium Calor (literally, heat of the throat, or sore throat) they prescribedgargling with a mixture of ingredients containing copper. Copper was also employed in 15PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

29. REWIEWOFLITERATUREancient India and Persia to treat lung diseases. The tenth century book, LiberFundamentorum Pharmacologie describes the use of copper compounds for medicinalpurposes in ancient Persia. Powered malachite was sprinkled on boils, copper acetate aswell as and copper oxide were used for diseases of the eye and for the elimination ofyellow bile Nomadic Mongolian tribes treated and healed ulcers of venereal origin withorigin with orally administered copper sulfate. It was reported that, during the choleraepidemics in Paris of 1832, 1849 and 1852 copper workers were immune to the disease. Turning to more modern times, the first observation of coppers role in theimmune system was published in 1867 when it was reported that, during the choleraepidemics in Paris of 1832, 1849 and 1852 copper workers were immune to the disease.More recently coppers role in the immune system has been supported by observationsthat individuals suffering from Menkes disease (an inherited disease in which there isdefective copper absorption and metabolism) generally die of immune system-relatedphenomena and other infections. Further, animals deficient in copper have been shown tohave increased susceptibility to bacterial pathogens such as Salmonella and Listeria.Evidence such as this has led researchers to suggest strongly that copper compounds notonly cure disease but also aid in the prevention of disease. In 1895, Kobert published his review of the pharmacological actions of coppercompounds. Copper arsenate had been used to treat acute and chronic diarrhea as well asdysentery and cholera. A variety of inorganic copper preparations were found to beeffective in treating chronic adenitis eczema, impetigo, scorphulosis, tubercularinfections, lupus syphilis, anemias, chorea and facial neuralgia. An organic complex ofcopper developed by Bayer was shown to have curative powers in the treatment of 16PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

30. REWIEWOFLITERATUREtuberculosis. Copper treatment for tuberculosis continued until the 1940s, and variousphysicians reported on their success in using copper preparations in intravenousinjections. Finnish copper miners were unaffected by arthritis as long as they worked inthe mining industry. In 1939, the German physician, Werner Hangarter, notice thatFinnish copper miners were unaffected by arthritis as long as they worked in the miningindustry. This was particularly striking since rheumatism was a widespread disease inFinland, and workers in other industries and other towns had more rheumatic diseasesthan did the copper miners. This observation led Finish medical researches plus theGermans, Hangarter and Lubke, to begin their now classic clinical trials using an aqueousmixture of copper chloride and sodium salicylate. They successfully treated patientssuffering from rheumatic fever, rheumatoid arthritis, neck and back problems as well assciatica. Until recently just as in Plinys time, the medical profession used copper sulfateas a means to clinically induce vomiting. This is based on the fact that one of the bodysnatural physiological responses to prevent copper intoxication is vomiting. A manual ofPharmacology and its Applications to Therapeutics and Toxicology, published by W.B.Saunders Company in 1957 recommends the use of 0.5gm of copper sulfate dissolved ina glass of water, in a single dose, or three doses, of three doses of 0.25gm fifteen minutesapart for this purpose. Since, 1934, it has been known that individuals suffering fromsuch diseases as scarlet fever, diphtheria, tuberculosis, arthritis, malignant tumors andlymphogranulomas exhibit an elevation of copper in their blood plasma. Since then, thelist of maladies bringing about such elevation has been extended to fever, wounds, ulcers,pain, seizures, cancers, carcinogenesis, diabetes, cerebrovascular and cardiovascular 17PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

31. REWIEWOFLITERATUREdiseases and irradiation and tissue stresses, including restricted blood flow. This suggeststhat this redistribution of copper in the body has a general role in responding tophysiological disease or injury stress. On the other hand, the elevation of copper in theaffected organ has led some to postulate that it was this excess of copper that caused thedisease. Nonetheless, this elevation of copper in diseased states is suggested to accountfor the natural synthesis of copper-dependent regulatory proteins and enzymes in thebody required for biochemical responses to stress. It may be that these natural coppercomplexes expedite the relief of stress and the repair of tissues. Thus, it appears that inaddition to the anti-bacterial and anti-fungal activity of inorganic copper compounds asrecognized by the ancients metallo-organic complexes of copper have medicinalcapabilities that are fundamental to the healing process itself.Literary reviewModern research abstracts on Tamra Few of research papers published in internet or elsewhere were done at thefollowing centres as highlighted. 1. Copper is necessary for formation of one of the apparent super power antioxidants, superoxide dismutase (SOD)*Its also critical for the creation of collagen, a core protein found in bones, connective tissues and skin.*Copper plays a role in blood pressure control, cholesterol and glucose metabolism and enzyme3. 2. Without copper scientists claim that cells cant produce energy, metabolize iron or detoxify free radicals. Without copper, we cant grow blood vessels, synthesize neuropeptides that control muscle contractions, or make the collagen that gives our skin its elasticity4. 18PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

32. REWIEWOFLITERATURE 3. Scientist has reviewed a wide variety of copper complexes that have potent anti inflammatory activity when administered to humans or animals5. 4. When copper supplements are given to animals or humans, the additional dietary copper has been found to lower carcinogenesis and tumor growth, inhibit the development of cardiovascular problems and revers many inflammatory effects6. 5. Copper and its complexes stimulate a protein control and scientists say that human embryos lacking control are aborted spontaneously7. 6. The first modern research on the subject of copper medicinal substances was by Prof. John R. J. Sorenson of the University of Arkansas for Medical Sciences, College of Pharmacy, W. H. O., in 1966, demonstrated that copper complexes have therapeutic efficacy in the treatment of inflammatory diseases using doses that are non toxic. *Copper alone have shown to prevent or even cure the ulceration of the stomach and intestines*Copper plays an important role in iron absorption and transport.*Copper is a component of or a co factor for approximately so different enzymes. These enzymes need copper to function properly8. 7. Copper is a necessity of for: --"cleaning" of the organism from the excesses of free radicals, biogenic amines and cholesterol --the proper synthesis of hemoglobin, elastin, collagen and probably thyroid hormones.*Copper provides the energy formed in the respiratory chain and needed for biochemical syntheses and proper physical activity9. 8. New biochemical and crystallographic evidence define copper as being necessary for structural and catalytic properties of cuproenzymes. *Mechanisms responsible 19PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

33. REWIEWOFLITERATURE for the control of cuproprotein gene expression are not known in mammals; however, studies using yeast as a eukaryote model support.The existence of a copper-dependent gene regulatory element. Diets in Western Countries provide copper below or in the low range of the estimated safe and adequate daily dietary intake. *Copper deficiency is usually the consequence of decreased copper stores at birth, inadequate dietary copper intake, poor absorption; elevated requirements induced by rapid growth, or increased copper losses. *The most frequent clinical manifestations of copper deficiency are anemia, neutropenia, and bone abnormalities. Recommendations for dietary copper intake and total copper exposure, including that from potable water, should consider that copper is an essential nutrient with potential toxicity if the load exceeds tolerances range of safe intakes should be defined for the general population, including lower safe intake and an upper safe intake, to prevent deficiency as well as toxicity for most of the population10. 9. Coppers role in connective tissue is linked to the enzyme lysyl oxidase. From a biochemical perspective, copper is a cofactor for the enzyme and a determinant of its activity in connective tissues. *Lysyl oxidase catalyses a post-translational oxidation of certain lysine and hydroxylysine residues. The peptidyl aldehydes so formed become active centre for the formation of cross-links in collagen and elastin. Less well understood is how copper controls the steady-state activity of lysyl oxidase; the enzyme fails in copper deficiency. *Giving copper to a deprived animal increases lysyl oxidase activity in aortic tissue. Such activation in vivo appears to require caeruloplasmin. Suspending aortic tissue in a copper-enriched 20PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

34. REWIEWOFLITERATURE growth medium also activates lysyl oxidase provided that tissue structure is kept intact. Activation in vitro occurs with the binding of copper to a large-molecular- weight component, presumably the enzyme. Binding will not occur if protein synthesis is blocked.*these studies clearly show that the synthesis of mature elastin and collagen can be controlled by the availability of copper. They further suggest that transport of copper to aortic tissue and its engagement to lysyl oxidase are linked to the synthesis or lysyl oxidase, an extracellular carrier, or both11. 10. Copper ions can adopt distinct redox states oxidized Cu(II) or reduced (I), allowing the metal to play a pivotal role in cell physiology as a catalytic cofactor in the redox chemistry of enzymes, mitochondrial respiration, iron absorption, free radical scavenging and elastin cross-linking. *If present in excess, free copper ions can cause damage to cellular components and a delicate balance between the uptake and efflux of copper ions determines the amount of cellular copper.*In biological systems, copper homeostasis has been characterized at the molecular.It is coordinated by several proteins such as glutathione, metallothionein, Cu-transporting P-type ATPases, Menkes and Wilson proteins and by cytoplasmic transport proteins called copper chaperones to ensure that it is delivered to specific subcellular compartments and thereby to copper-requiring proteins12. 11. Copper is required for infant growth, host defense mechanisms, bone strength, red and white cell maturation, iron transport, cholesterol and glucose metabolism myocardial contractility, and brain development. *Copper deficiency can result in 21PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

35. REWIEWOFLITERATURE the expression of an inherited defect such as Menkes syndrome or in an acquired condition. Acquired deficiency is mainly pathology of infants; however, it has been diagnosed also in children and adults.*Lost cases of copper deficiency have been described in malnourished children. The most constant clinical manifestations of acquired copper deficiency are anemia, neutropenia, and bone abnormalities.Other, less frequent manifestations are hypopigmentation of the hair, hypotonia, impaired growth, increased incidence of infections, and alterations of phagocytic capacity of the neutrophils, abnormalities of cholesterol and glucose metabolism, and cardiovascular alterations. *Measurements of serum copper and ceruloplasmin concentrations are currently used to evaluate copper status. These indexes are diminished in severe to moderate copper deficiency; however, they are less sensitive to marginal copper deficiency. Erythrocyte superoxide dismutase and platelet cytochrome c activities may be more promising indexes for evaluating marginal copper deficiency13. 12. The recognition of disordered copper metabolism simulating a deficiency state--as occurs in Menkes KHS and in variant Elhers-Danlos syndrome--has important implications.*The full description of the relationship that thionein and other intracellular proteins might have in the etiology of these alterations has yet to be written.*The elegance of the interplay of biochemical defects, physiological dysfunction, and clinical manifestations in copper metabolism is virtually unmatched in nutritional biology; yet, our present abilities to determine human copper status are limited.*Now that it is clear that intracellular redistribution as well as total-body depletion can effect the disruption of copper-dependent 22PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

36. REWIEWOFLITERATURE functions, a concerted effort to improve status assessment through the use of functional indices should become a high priority.Finally, the pursuit of the bases of coppers involvement in host defenses, antiotoxidant protection and carbohydrate metabolism--functions in which clear links to established mammalian cuproenzyme are at present elusive--should provide exciting substrate for investigators for years to come14. 13. Metabolic balance studies have demonstrated that daily copper losses are approximately 1.3 mg/day. *In order to remain in copper balance, the average adult male must consume a diet which contains at least 2 mg copper/day. *It has been assumed that most diets satisfy this requirement because of the ubiquitous presence of copper in most foodstuffs. Recent studies, however, have shown that dietary copper may often fall below the estimated daily needs. *Nevertheless, clinically evident copper deficiency has been documented in only a few situations.of these disorders. Menkes syndrome has been most intensively studied. This x-linked abnormality is associated with copper deficiency due to impaired gastrointestinal copper absorption. *However, the clinical disorder cannot be corrected readily with copper replacement, thus suggesting that Menkes syndrome may reflect more than simple copper deficiency. *Nutritional copper deficiency appears to be well documented in two situations: *The newborn, usually premature, undergoing rapid growth on a diet poor in copper, and the patient maintained on total parenteral nutrition for long periods of time without copper supplementation. *In both of these situations, anemia and neutropenia are the most striking hematologic abnormalities associated with 23PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

37. REWIEWOFLITERATURE copper deficiency. Sideroblastic changes as well as nuclear maturation defects observed in erythroid precursors. However, suggest that there is an effect of copper deficiency on the hematopoietic system which cannot be explained solely by defective plasma iron transport15. 14. Anaemia, osteoporosis and scurvy-like bone changes are recognized in the deficiency, and they respond to copper. Copper intake is falling in western countries as a result of prepackaging of foods, and low-grade chronic deficiency may become a problem. *The features seen in Menkes syndrome suggest that human beings may be rather susceptible to the vascular and neurological effects of copper deficiency; *These effects may be encountered as a consequence of prolonged mild copper deficiency. Measurement of the serum concentrations of caeruloplasmin before and after moderate copper repletion is suggested as a method of detecting mild copper deficiency16. 15. Studies of two copper proteins, ceruloplasmin and its recently discovered homologue hephaestin, have provided two molecular links connecting the pathways of copper and iron metabolism. The recent identification of other proteins of iron and copper metabolism, for example, copper ATPases and the membrane iron transporters DCT1/DMT1/Nramp2 and IREG1/MTP1/ ferroportinl, are likely to fill crucial pathway gaps. *The ongoing discovery of genes and gene mutations involved in the metabolism of copper and iron provides an important key to a deeper understanding of the connections between the pathways, and their physiological and pathological consequences17. 24PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

38. REWIEWOFLITERATURE 16. Copper is one of the essential trace elements. It is part of a number of enzymes. Deficiency of the element is manifested by impaired haematopoesis, bone metabolism, disorders of the digestive, cardiovascular and nervous system. Deficiency occurs in particular in patients suffering from malnutrition, Malabsorption, great copper losses during administration of penicillamine. S Sporadically copper intoxications are described (suicidal intentions or saccidental ingestion of beverages with a high copper content). *Acute exposure to copper containing dust is manifested by metal fume fever. *Copper salts can produce local inflammations. Wilsons disease is associated with inborn impaired copper metabolism.*In dialyzed patients possible contaminations of the dialyzate with copper must be foreseen as well as the possible release of copper from some dialyzation Membranes.With the increasing amount of copper in the environment it is essential to monitor the contamination of the environment18. 17. Although the nutritional essentiality of copper was established in 1928, a preoccupation with hematology delayed the discovery of cardiovascular disease from copper deficiency for more than a decade. *Anatomical studies of several species of deficient animals revealed, interalia, aortic fissures and rupture, arterial foam cells and smooth muscle migration, cardiac enlargement and rupture, coronary artery thrombosis and myocardial Infarction. *Abnormal biochemistry in deficiency probably contributes to these lesions, e.g., Decreased activities of lysyl oxidase and superoxide dismutase which result in failure of collagen and elastin crosslinking and impaired defense against free radicals. *Copper deficiency also decreases copper in hearts and other organs and cells and 25PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

39. REWIEWOFLITERATURE increases cholesterol in plasma. *Abnormal physiology from deficiency includes abnormal electrocardiograms, glucose intolerance and hypertension. *People with ischemic heart disease have decreased cardiac and leucocyte copper and decreased activities of some copper-dependent enzymes.*Copper depletion experiments with men and women have revealed abnormalities of lipid metabolism, blood pressure control, and electrocardiograms plus impaired glucose tolerance.*The Western diet often is as low in copper as that proved insufficient for these people. Knowledge of nutritional history can be useful in addressing contemporary nutritional problems19. 18. Copper deficiency during embryonic and fetal development can result in numerous gross structural and biochemical abnormalities. *Such a deficiency can arise through a variety of mechanisms, including low maternal dietary copper intake, disease-induced or drug-induced changes in maternal and conceptus copper metabolism, or both. *Current data suggest that changes in free radical defense mechanisms, connective tissue metabolism, and energy production can all contribute to the dysmorphogenesis associated with developmental copper deficiency20. 19. The identification by Danks that Menkes syndrome, a genetically determined defect in copper absorption and utilization, is responsible for the observed clinical manifestations provided further insight into the physiopathologic effects of copper deficiency21. 26PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

40. REWIEWOFLITERATUREDRUG REVIEW:Tamrotpatti: *According to most of Rasa texts Tamra is considered as Shukra of Kartikeya whichfell on ground and thus the Utpatti of Tamra. *According to Jothishya Shastra and Parada Samhita, the Surya Kiranas TejoBhaga turned into Tamra. *According to Varaha Purana: 7000 yrs back to the date of Varaha Purana Tamratook its birth and the mythology says that - A Rakshasa by name Gudakesha who was bound with a handsome body like Tamrameditated on Lord Varaha for 14,000 yrs for which Lord Varaha was pleased and askedfor the Varan for which Gudakesha requested that he would wish to die by theSudarshana chakra of Lord Varaha and his body after death should turn in to Tamra AdiDhatu and this metals should be for any Mangalya kara, Pavitrata and serve the Lord inall means. After this request Lord Varaha killed Gudakesha with his Chakra on Vaishakamasa, Shukla Paksha, Dwadashi in Abhijit Lagna and the Gudakeshas body fell down onearth and his Mamsa turned into Tamra, Rakta into Swarna, Asthi into Roupya andsimilarly many Dhatus took their birth also by the Mala the metals like Sesa, Kamsya,Ranga, Riti etc. took their birth on earth. Thus on this back ground of Varaha PurnaTamrotpathi can be confirmed in regard to its Utpathi on earth on Vaishaka Masa, ShuklaPaksha Dwadashi in the Abhijit Lagna. 27PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

41. REWIEWOFLITERATURETable No-1.SYNONYMS of Tamra22-30:Sl.No Name R.K. R. R. R.T B.R. R.J. A.P. Dh R B. D S. Ni N N. mr P. S.1 Anuvindam +2 Ambakam + + +3 Aravindam + +4 Arkam + + +5 Arkestam +6 Arakta7 Udumbara + + + +8 Udambaram + +9 Udubaram + + + +10 Unduvaram +11 Ushmam12 Ushmakaram13 Audumbaram + +14 Audumbaram +15 Aunduvaram + +16 Kaniyasam +17 Koniyasam +18 Kamalahvayam +19 Karendudha20 Kamodam21 Kalamardonan22 Konyasm +23 Krukashom24 Charavindam +25 Tapanestam + +26 Tamram + + + + + + +27 Tamrakam +28 Twastram + +29 Trilocanam30 Tryambakam + + + +31 Tryambakadistam32 Twistam + +33 Dwyastam +34 Nagasyamardanam35 Nilavatam36 Nypaliyam +37 Nepalakam + +38 Pavitram +39 Pavitrakam + 28PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

42. REWIEWOFLITERATURE40 Brahma Varchasam +41 Brahma Vardhanam +42 Bahirstam43 Brahmam +44 Bhaskaram +45 Mrudambaram +46 Markatasyam +47 Manmatha48 Maraha49 Mihirahvayam +50 Munipittalam +51 Mleccham +52 Mlecchamukam + + + + +53 Mlecchavaktram +54 Mlecchasyam +55 Raktam +56 Raktakam + + +57 Raktadhatuhu + +58 Raktadhatukam + +59 Raktaloham +60 Ravipriyam + + + + + +61 Raviloham + +62 Rajeevam +63 Lohitayasam + + + +64 Vamnam65 Varistam +66 Vaaristam67 Vantikam68 Vishadam69 Vishnasanam70 Vyastam +71 ShabanaBhedakym +72 Shulvam + + + + + + + +73 Sadaham74 Sidham75 Sarvaloham + +76 Suryaparyaya + + Samgnakam77 Suryaloham + +78 Suryakyam +79 Suryagam + +80 Suryestam +81 Hemagarbham 29PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

43. REWIEWOFLITERATUREName in different language31.32: 1. Arabic Nuhas, Nahas, Nohas, Nohassa, Naahas 2. Italian Rame 3. English Copper 4. Kannada Tamra, Tambra 5. Kineeya Venas 6. Konkani Tambe 7. Gujarati Trambu, Tambu, Trambo 8. Chini Chintung, Tung, Chaikin 9. Germany Capher, Cuper 10. Tamil Tampram, Chembu, Sembu, Senabu 11. Telugu Ragi, Tamramu, Samba 12. Dinemar Cobar 13. Palendi Miyej 14. Spanish Camber 15. Punjabi Neeltuseya 16. Pharasees Cuiber, Cuibre 17. Farsi Meesa, Mees 18. Barmi Keyeni, Keyani, Kyani 19. Bangla Tama, Tam, Tamba 20. Bhutani Jang, Jamgata, Neeltokar 21. Marathi Tambe, Tamra 30PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

44. REWIEWOFLITERATURE 22. Malayalam Chempu, Tamram 23. Rusi Crensayajedjed 24. Latin Cuppram 25. Sindhi Tamb 26. Swedish Copper 27. Dutch Copper 28. Ilibru Nehoset 29. Hindi Tamba, Tama, TammaPrapthi Sthana33: As per the classics only two places Nepala and Mleccha is available. Nativecopper occurs in nature only sparadically, the golden yellow sulphide of copper beingmore commonly available. These have a coating of green malachite and blue azurite(carbonates) which are green carbonates formed by alteration of the sulphide. Bothmalachite and azurite thus often indicate the presence of enriched sulphide below thesurface. The chief producing areas have been districts of Singhbhum (Bihar), Jhanjhunu,Alwar and Udaipur (Rajasthan); and Balaghat (Madhya Pradesh). The domesticproduction of copper metal continued to remain much short of requirement in thecountry. The HCL projects, namely Khetri Copper Complex (KCC) in Rajasthan andIndian Copper Complex (ICC) in Bihar and a copper mining cum concentrator projectof Malanjkhand in Madhya Pradesh. Copper, according to Indian Bureau of Mines, wasmainly consumed in cable winding wires and semis and alloys end use sectors, whichtogether accounted for 82% of the total consumption in 1986. Other important end use 31PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

45. REWIEWOFLITERATUREsectors were auto ancillary, electricals, coinage, defence, chemicals, railways, chemical die casting etc. and these together consumed 18%.Around the World34: Best crystals are found in the Keweenawar Peninsula, Lake Superior (USA)where huge masses occur; other include Monte Catini (Italy), Bisbee, Arizone, Franklin,New Jersey (USA) and Langbar (Sweden) and in Chile, Germany, USSR and Zambia.Chemical symbol35 - CuTypes and Character36.37 1. NepalCharacter -- Susnigdha, Mrudula, Rakta varna, Ghanaghatakshama, Guru,Nirvikar, Amla, Swacha Lohangudi rahita, Rasakarma poojita, Guna sresta. 2. MlechaCharacter Ruksha, Katina, Sitha, Krishana, Aruna Yama, Athivamaka,Ghanaghataakshama, Kshalitha cha punaha Krishna.PharmocodynamicsTable No-2 RASA of Tamra38-47:Sl.No. References Madhura Amla Lavana Katu Tikta Kashaya1 Rasa jala nidhi + + + +2 Rasa ratna + + + + samucchaya.3 Rasamritam + + + +4 Rasendrasara sangraha + + + +5 Rasa ratnakara + +6 Rasa kama dhenu + + +7 Ayurveda prakasha + + + +8 Bhava prakasha + + + +9 Siddhabheshaja + + + + manimala 32PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

46. REWIEWOFLITERATURE10 Rasa tarangini + + + +11 Siddha yoga sangraha + + + +12 Dhanwantari nighantu + + +13 Raja nighantu + + +Table No-3 GUNA of Tamra48-53:Sl Guna Referenceno1 Laghu,Sara,Snigdha. Ayurveda prakasha,Bhava rakasha, Rasa tarangini, ,Siddha bheshaja manimala Rasa Jala nidhiTable No-4 VIRYA of Tamra54-63: Sl no Shita virya Ushna virya 1 Rasajala nidhi Rasendra chudamani 2 Yoga rathnakar Ananda kanda 3 Rasa ratnakara Rasa kamadhenu 4 Ayurveda prakasha Rasa ratnakara 5 Nighantu shiromani Rasa tarangini 6 Louha Sarvasavam Siddha yoga sangraha 7 Bhava prakasha Rasamritam 8 Dhanvantari nighantu Rasa ratna samucchaya 9 Raja nighantu Rasendra sara sangrahaTable No-5 VIPAKA of Tamra64-71:Sl.No Vipaka Reference01 Madhura Rasendra chudamani, Anada kanda, Rasa ratna samucchaya, Rasa tarangini, Siddha yoga sangraha.02 Amla Sidda bhisaja manila03 Katu Raja nighantu, Ayurveda prakasha, Dhanvantari nighantu, Bhava prakasha, Sidda bhisaja manila. Rasa jala nidhi 33PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

47. REWIEWOFLITERATURETable No-6. KARMA of Tamra72-80 KARMANI C S.S. R.C R. R.K. RJ. R. R A B. S.B. B Y. . SS D. N. R. T P P M R R S . S Arogyam Ayushyam + Alpa + + + brimhanam Urdhwadhah + + + + parishodhana Kshut karam + + + Jara mrityu shamanam Netryam + + + + + Deepanam Rasayana + +, Ruchya + + + Ropanam + + + + + + Lekhanam + + + + + + + + + + + + Saram + + Sarakam + + +Tamra grahya laxana81 Susnigda mrudula shona ghanaghathaksma guru nirvikar guna sresta tamraThese properties are belongs to Nepal variety It is consider good quality Tamra a. Ghanaghatasaha i. e., by hitting the metal by a hard object it turns into a sheet like and never breaks which suggests the malleability and ductility of copper high percentage in the best sample. b. Suchikkanam suggests by touch it is slimy suggests the moulded metals turn into a uniform smooth surface after cooling to room temperatures again suggests the concentration of copper with high percentage. 34PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

48. REWIEWOFLITERATURE c. Appears as Japakusuma Varna which suggests the colour of a extracted copper or a mother native copper. d. Mridu suggests that the metal soft and can be moulded to any shape due to its malleable nature and does not break suggesting the high percentage of copper which has ductile nature. e. Best used in Chiktsa is said to be best Tamra, suggestive of high concentrated copper when taken for clinical trials with a nontoxic dose is best as medicinal use. f. The Tikakara of Rasa Tarangini mentions that it should be Mala Rahita or Lohanagadi Rahita suggesting the pure copper with no other alloys or adulterants should be taken for the study.Tamra agrahya laxana82 Shitha Krishnavarnachaya, athivami katorakama kshalitha cha puna krishna.Shita gunayukta: Coldness, Katoraka: Hardness.Krishnatva: In generally the colour of copper is black colourAthivami: After proper marana of this Tamra leads to severe vomitingKshalitha cha punaha krishntha: After washing of copper again regain black colourThese properties consider as Mlecha tamra this is unsuitable Medicinal purposeUses: Kapha pitta nashaka, Udara roga, Kusta, Meha, Amadhosha, Yakrut pleharoga, Shoola, parinam shoola, Arsha, Kshaya, Amla pitta, Pandu, Swasa kasa Jwara,Sthoulya, Grahani, Shotha, Pinasa, Netra roga, Vata roga.Toxic effect of tamra:83.84.85 Na Visham Vishamithyastamra cha Visha Muchyate Eko dosho vishwasto doshasta Tamra Prakashite. 35PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

49. REWIEWOFLITERATURE Bramo Murcha Vidhata cha uthakiede Shosha Vanthya Aruchi santapa ethe dosha vishopama Ayugnaha kanti viryabalanashaka Vamana murcha brama utkleda kusta shoola The objects aimed at Sodhana are: - It separates physical and chemical impurities. - It converts heterogeneous state to homogenous state. - Detoxification of toxic qualities of the drug. - It enhances the potency of drug. - Hard substances are converted into soft. - Adulteration of the drug is removed.Sodhana is of two kinds: (1) Samanya Sodhana; 2) Vishesha Sodhana Before going for Marana, a prime important processing known as TamraShodhana is a must as the available Tamra may have few of adulterants, alloys, foreignbodies etc. in it which might cause ill effect. So that considering which most of theAcharyas have mentioned various Lakshanas which appear. In few of them are enlistedherewith.Table No-7.Ashuddha Tamra Doshas86-91Sl. Doshas A. R. Y.R. Ra. R. B.P. R. R. Dh. B.R.No P T. Chu K. R. J. N D S N1 Arati +2 Aruchi + + + + +3 Ayurnaktuam + + +4 Utkleda + + + + +5 Utklesha + + +6 Udreka 36PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

50. REWIEWOFLITERATURE7 Kandu x8 Kantignatva + + + +9 Kamala10 Kushtam + + +11 Klama +12 Kledanam + +13 Gadotkleda +14 Gatratapa +15 Chittatapa + +16 Chittasantapa + + +17 Jivakshaya +18 Tapa +19 Daha + + + + + + + +20 Dehanasha +21 Dhatushasha +22 Dhatukshaya +23 Nana Ruja24 Nanagadanam Sahayakartrutwa25 Balapahatvam + +26 Medaha + + +27 Bhrama + + + + + + + + +28 Bhranti29 Murccha + + + + + + + +30 Moha + + + +31 Rekaha +32 Vami + + + + + + + +33 Vatasram34 Virekah + +35 Vividharoga36 Vishamaruja +37 Viryapahatwa + +38 Shotha + +39 Shosha + + + +40 Aamajashasha + +41 Sweda + + +42 Samastasoshaha +Also in few contexts of the various texts Tamra is explained as Visha or even more than aVisha like in Rasendra Sara Samgraha also in Rasansutam the Doshas are mentioned andhenceforth Shodhana is absolutely necessary. 37PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

51. REWIEWOFLITERATUREBecause by Shodhana 1. Visible and invisible Doshas get away i. e. the Bhaotika Ashuddhis get rid by Shodhana. 2. As Tamra is a metal we cant directly process it into Marana for which Tamra turns into brittle form thus helpful of Marana. 3. By Shodhana Samskara Guna Vardhana occurs. 4. Any of other metals or alloys in Tamra gets rid by Shodhana. Also in the classics its even mentioned that Shuddha Tamra in Amrutatulya whereas Ashuddha Tamra is Vishatulya.Samanya Shodhana of Tamra92. isiauqUlVq Msije| qwcrmi SuSu i xmiS|| xuhSsWmh zUw mzxri||1. According to Rasa Ratna Sammuchchaya: All Dhatus are heated and quenched for 7 times successively in Taila, Takra, Gomutra, Aranala and Kulattha Kwatha. Similarly is the opinion of Rasa Ratnakara, Ra. Chi and R. S. S. 2. According to Riddhi Khanda of Rasa Ratnakara: All Dhatus are heated and quenched for 7 times successively in Taila, Takra, Gomutra, Konji and Ravidugda. 3. According to Rasa Paddhati Parada/ 49: All Dhatus are heated and quenched for 7 times in the following order as Takra, Kanji, Gomutra, Tilataila and Kulattha Kwatha. 38PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

52. REWIEWOFLITERATURE 4. According to Rasa Kamadhenu 2/1/10: All Dhatus heated and quenched for 7 times in Kadalimoda Swarasa. 5. According to Rasa Manjari 1/53: All Dhatus by Bhavana in Jambiri Swarasa and Karkotishringijala becomes Shuddha. 6. According to Rasa Hridayatantra Prathamavabhoda: Bhavana of Dhatus with Kshara then Sneha and lastly with Amla Dravyas make them Shuddha.Vishesha Shodhana of Tamra93. As per the opinion of Ayurveda Prakasha 3/117 and other authors even afterSamanya Shodhana it should be processed with Vishesha Shodhana for enhancing itsproperties. By Samanya Shodhana certainly there are changes in metallic nature but fortherapeutic processing it should be always processed with Vishesha Shodhana by whichif at all any of residual Doshas get rid. By processing with specific media or drugsspecific Dosha Nirharana is been explained as mentioned herewith.Vishesha shodhana94.i Saindava nimba lepita tamra patra---Tapta--- Nishechana in niregundiii. Saindava nimba lepita tamra patra---------- Nishechana in kanjiiii.iii.Tamra churna gomutra ---- Madyamagni paka jala prakshalanaiv. Arkadugda saindava lavana lepita tamra patra--- Tapta ---Nishechana in niregundi95.Table No-8. Tamra Shodhana Reference Drugs ProcedureRasarnava 7/106 Snuhi Ksheer, Arka Ksheer, Agni Pratapta and Lavana, Kshara, Amla Lepa Nirgundiras NimajjanaRasa Hridaya Tantra 9/14 - Agni Pratapta and Nirgundiras NimajjanaRasa Ratna Samuchchaya Ksharamla Agni Pratapta and Dalana5/49 into Mahishi Takra for 7 times 39PHYSICO-CHEMICAL ANALYSIS OF SAMANYA & VISHESHA SHODITA TAMRA AND TOXICOLOGICAL STUDY OF TAMRA BHASMA

53. REWIEWOFLITERATURERasa Ratna Samuchchaya Saindhava lavana and Agni Pratapta and5/51 lemon juice Nirgundiras NimajjanaRasendra Sara Sangraha Gomutra Boil for 3 hours1/271Rasendra Sara Sangraha Saindhava lavana, Arka Agni Pratapta and1/272 Dugdha lepa Nirgundiras NimajjanaRasa Ratnakara 8/47-49 Lavana, Snuhi Ksheera, Agni Pratapta and Arka ksheera & Khatika, Nirgundiras Nimajjana for Saindhava, Takra, Aranala 12 times Agni Pratapta and Nimajjana in Kanjiyukta NirgundirasRasendra Chudamani 14/46 Kanji