Abstract
The metal, Tamra though mentioned in Ayurveda with a wide range of therapeutic utilities; is attributed with Ashta Maha Dosha. Hence, one should be cautious while using Tamra Bhasma. Considering the significance of Tamra in therapeutics, many studies have been carried out at different centers of India. Aim of the present study was to compile such available research works done on Tamra in the Department of Rasa Shastra and Bhaishajya Kalpana (RS and BK), IPGT and RA, Jamnagar and provide brief information about pharmaceutical, analytical, and pharmacological studies. Total eleven studies on Tamra Bhasma, which revalidated the impact of classical guidelines, safety issues, and therapeutic utilities, were screened from PG Department of RS and BK, Institute for Post-Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar. All studies revealed that Tamra Bhasma is safe clinically, experimentally at Therapeutic Equivalent Dose (TED) levels as no toxic hazards were reported during the treatment period. In all aspects (pharmaceutical, pharmacological, and clinical) Somnathi Tamra Bhasma has proven to be better than Tamra Bhasma. The clinical efficacy of Tamra Bhasma has been evaluated in Shvasa, Kasa, Yakrit Pliha Vriddhi, Grahani, etc. conditions. Satisfactory responses with a decrease in the intensity of signs and symptoms were reported in all the studies. Though certain limitations were observed in these researches, the results can be considered as a lead for further well stratified studies covering larger population. No adverse effects were reported in any of these studies.
Keywords: Bhasma, Grahani, Rasa Shastra, safety, Somanathi Tamra, Tamra toxicity
Introduction
Since the prehistoric period, man has been using different sources of drugs for protection of health and treatment of diseases. These drugs in Ayurveda are obtained from natural sources such as plants, animals, and minerals. Use of metals and minerals in therapeutics has been found since Vedic period, which became an important part of Ayurvedic therapeutics due to their additional advantages like smaller doses, quick action etc.[1] Bhasmas are microfine powders of incinerated metals and minerals that are therapeutically useful in different disease conditions since centuries without developing any noticeable side effects. Though these Bhasmas are being safely practiced in Indian scenario, concerns are being raised on safety issues in the recent past.[2] At the same time a number of studies have been conducted in different institutes of India, which provided safety aspects of Bhasma. Metals and minerals are the integral part of therapeutics in Ayurveda and Tamra (copper) is one of such metals, which, if properly processed and detoxified is useful in many diseases.[3] But if not processed properly, is dangerous to life.[4] It's toxic nature in improperly purified or incinerated state has been described as Ashtamahadoshas (eight blemishes) in Ayurvedic classics.[5] To make it fit for therapeutic use, Tamra has to pass through a set of classical pharmaceutical processes known as Shodhana (purification), Marana (incineration), and Amritikarana. Tamra Bhasma is useful in the treatment of Udara (ascitis), Pandu (anemia), Shvasa (bronchial asthma), and Amlapitta (hyperacidity), etc.[6]
Considering the wide therapeutic utility of Tamra Bhasma, many research works have been carried out in the Department of Rasashastra and Bhaishajya Kalpana (RS and BK), Institute for Post-Graduate Teaching and Research in Ayurveda (IPGT and RA), Gujarat Ayurved University, Jamnagar with an intention to revalidate the classical principles of therapeutics.
The present study was to compile all available research works done on Tamra in the Department of RS and BK, and provide brief information about pharmaceutical, analytical, and pharmacological contributions.
Materials and Methods
Works carried-out in the Department of RS and BK, IPGT and RA, Gujarat Ayurved University, Jamnagar at PhD and PG levels during 1964-2011 were compiled and screened to revalidate the classical concepts of drug preparation.
Observations and Results
Initial studies carried out in 1964 evaluated clinical efficacy of Tamra Bhasma[7] in cases of Shvasa and Amlapitta.[8] The drug was administered at a dose of 65-125 mg. along with honey and other herbal powders such as Guduchi (Tinosporia cordifolia Willd.), and Amalaki (Phyllanthus embilica Linn.). Encouraging results were obtained in this preliminary study.
Another study in 1965 evaluated clinical efficacy of Tamra Bhasma[9] and Somnathi Tamra Bhasma[10] (STB) on Shvasa (bronchial asthma), Kasa (cough), Yakrit-Pliha Vriddhi (hepato-spleenomegaly).[11] Tamra Bhasma is reported to contain 37% Cu, while STB contains 24% Cu and traces of arsenic (80 ppm). Tamra Bhasma was administered in five clinically diagnosed cases of Shvasa for 30 consecutive days in a dose of 65 mg. along with Talisadi churna and Madhu. STB was administered for 30 consecutive days in six clinically diagnosed cases of Shvasa in a dose of 125 mg. along with Pippali churna and Madhu. Both the drugs were found to be significant in relieving the signs and symptoms of Shvasa. Both the drugs were also administered in cases of Kaphaja Kasa and Yakrit Pliha Vriddhi with promising results. On comparison of the clinical efficacy, STB was reported to have better results over Tamra Bhasma.
Pharmaceutical study of Tamra Parpati[12] and its clinical efficacy on Yakrit Pliha Vridhhi and Grahani Roga was evaluated in 1968.[13] Tamra Parpati was administered to the patients of Yakrit Pliha Vridhhi and Grahani in a dose of 65-250 mg twice a day with Madhu and other suitable adjuvants like Takra for 30 days. The size of the enlarged liver and spleen was found to be reduced up to 65% with the administration of Tamra Parpati. Relief was also reported by the patients of Grahani.
Role of marana media in the preparation of Tamra Bhasma[14] was studied during 1988.[15] Bhasma was prepared by using three different medias (Parada, Gandhaka, and Kantakari). Gandhaka (sulfur) was reported to be the simplest and precise media in securing safe media in preparing Tamra Bhasma. Difficulties were expressed by the researcher while preparing Tamra Bhasma in the presence of Parada media. It was also reported that, Tamra Bhasma prepared with Parada did not pass the curd test[16] and hence remaining both groups were used clinically in Tamaka Shvasa at the dose of 125 mg thrice a day along with honey for 21 days. Tamra Bhasma showed significant results in Tamaka Shvasa. Total symptomatic relief observed by Tamra Bhasma of Gandhaka and Kantakari (Solanum xanthocarpum) media are 96.3% and 90.8% respectively. X-ray reports of chest posterio anterior view have shown good responses including reduction in thickening of broncho-vascular marking in both groups.
Studies in 1991[17] attempted on revalidating anti-asthmatic activity of Dhattura Mulatvak Swarasa Bhavita Kajjali, Gandhaka Marita Tamra Bhasma,[14] and Mallasindura.[18] Comparative study of these three Yogas was done on 56 known patients of Tamaka Shvasa for 21 days. Tamra Bhasma was given in the dose of 125 mg thrice a day along with honey. In this group, 86.16% and 87.22% relief in main and associated symptoms were found. An increase in peak expiratory flow rate was reported in Tamra Bhasma group. Breath holding time was well responded to Dhattura Mulatvak Swarasa Bhavita Kajjalli. Maximum increase in chest expansion and hematopoietic action was found in Mallasindura group. From the overall effect of the three Yogas, it was concluded that Tamra Bhasma provided better results in pacifying the signs and symptoms of Tamaka Shvasa.
Experiments on Tamra, Loha, Naga, Vanga, and Yashada Bhasmas with respect to their media and to identify the composition and genuinity were carried out in 1991.[19] This study highlighted the importance of media used in the preparation of different Bhasmas. Parada media was used in preparation of Tamra Bhasma.[9] Classical parameters such as Varna, Varitaratva, Rekhapurnatva, and contemporary parameters such as chemical analysis, Namburi phased spot test, ICP-AES (Inductively Coupled Plasma Atomic Emission Spectroscopy) were used for evaluation of Bhasmas. On chemical analysis, acid insoluble ash 5.67% and 67.50% copper as Cu was found in Tamra Bhasma. Spectroscopy detected trace elements such as Ba, Cd, Hg, K, and Mg. Study revealed that Bhasmas prepared in different media having different compositions and thus show different chemical reactions.
Trial for pharmaceutical standardization of STB[10] was done in 2004.[20] Two samples of STB were prepared by Kupipakva method, one in Valuka Yantra and the other in electrical muffle furnace (EMF). EMF method was found more suitable than classical Valuka Yantra method considering the percentage yield of STB and other advantages of EMF. Manufacturing process of STB has been standardized in terms of time (total duration of 12 h) and temperature (Mridu Agni - 120-250°C, Madhyama Agni - 250-450°C, and Tivra Agni - 450-630°C). Analytically both samples of STB were found to contain Cu, As, S, and Fe. In addition, presence of Hg was reported (8.24%) in STB prepared in EMF while it was not found in the sample prepared in Valuka Yantra. This data reflects that, there is a difference in the chemical composition of both the samples prepared by different methods. Further, toxicity studies have been attempted in experimental animals. Chronic toxicity with five Therapeutic Equivalent Dose (TED) of both samples has shown mild degenerative changes in heart, kidney, liver, and spleen. Comparatively STB prepared in Valuka Yantra was reported to be safe in the study. Though the samples are showing mild degenerative changes at five TED levels, they may be safe at TED levels.
Attempts to develop pharmaceutical profile and provide evidence about safety of Tamra Bhasma[21] and STB[10] on the basis of pharmacological grounds were done in 2005.[22] Pharmaceutically preparation of STB was found quite easier than Tamra Bhasma. Acute and chronic toxicities were studied in experimental animals. No mortality was reported in acute toxicity study even at 30 TED of Tamra Bhasma and STB. Chronic toxicity study with five TED has shown mild fatty degenerative changes in kidney, liver, and heart. However, these changes were observed only in kidney and heart with the treatment of STB. Both the drugs were used clinically in 12 patients of Medoroga. 30 mg of Tamra Bhasma twice a day with water for 21 days has shown a significant decrease in serum cholesterol and serum triglyceride levels. 75 mg of STB twice a day has found highly significant in decreasing serum triglyceride and high density lipoprotein level. This validated Lekhana Karma and lipid lowering capacity of STB. This activity was found significant in comparison to Tamra Bhasma.
Trial to develop standard manufacturing procedure of Tamra Bhasma by using Rasa Bhasma (Kajjali, Rasa Sindura, and Rasa Parpati) as media was done in 2006.[23] Bhasma was found to be cupric oxide in nature and associated with 30 other elements in different compound forms. In acute toxicity study, no exitus even at dose 16 TED was found, establishing the safety of the Bhasma at TED. Chronic toxicity studies (of 30 days duration) also established safety of Bhasma at five TED levels. Overall analysis of histopathological study indicates increased, though only modest, toxicity potential in Tamra Bhasma by Rasa Sindura media in comparison to other two groups. Clinically Tamra Bhasma prepared with Kajjali media was found better than Tamra Bhasma prepared with Rasa Sindura media in cases of Sthaulya (obesity).
Anti-hyperlipidemic and cardio-protective activity of Tamra Bhasma[21] and STB[10] in experimental models were evaluated in the studies of 2009.[24] Tamra Bhasma is identified as copper oxide (CuO); however, copper manganese oxide (CuMn2O4) was found in minor phase, whereas STB is reported to be a compound of copper, mercury, arsenic, and sulfur identified as aktashite (Cu6Hg3As4S6). Anti-hyperlipidemic activity and cardio-protective activities of STB were found significant in comparison to Tamra Bhasma. Significant decrease in serum triglyceride levels was reported with the treatment of Tamra Bhasma. The effect was statistically highly significant with STB in comparison to cholesterol control rats.
Trials on preparation of Tamra Bhasma[25] with Kajjali as media were done in 2011.[26] To evaluate the impact of Shodhana and establish safety, toxicity profile and anti-hyperlipidemic activity in experimental animals, Tamra Bhasma was prepared with Shodhita and Ashodhita Tamra. ICP-AES revealed that Tamra Bhasma prepared from Shodhita Tamra contained 56.42% copper and 23.06% sulfur while Bhasma prepared from Ashodhita Tamra (99.9% pure copper) had 44.91% copper and 45.35% sulfur. Traces of manganese, lead, arsenic, and zinc were found in both samples. Phase identification by X-ray diffraction revealed copper sulfate hydroxide [Cu4SO4(OH)6] and copper sulfide (CuS) in both samples of Bhasma, respectively. It was opined that, presence of hydroxide in Shodhita Tamra Bhasma sample may be due to mishandling of the sample. Tamra Bhasma, which did not undergo Shodhana procedures, took more Putas for preparation of Bhasma indicating that Shodhana procedure helps in easy and early preparation of Bhasma by increasing brittleness of Tamra and reducing hardness and particle size. No mortality was observed in acute toxicity study with both the samples even at 180 TED levels. Tamra Bhasma prepared from Shodhita Tamra was reported to be safe in the sub-chronic study (of 45 days). In contrast, Bhasma prepared from Ashodhita Tamra was found to be toxic even at TED levels. Bhasma prepared from Shodhita Tamra has shown significant anti-hyperlipidemic activity which is almost absent in Bhasma prepared from Ashodhita Tamra. Exact reasons behind this profile need to be ascertained by adopting suitable analytical parmeters. This study focuses on the role of Shodhana procedure in preparation of good Tamra Bhasma.
Discussion
Metals are used in various disease conditions from Vedic period, but their use increased after development of Rasashastra, which is an integral part of Ayurveda. Bhasma of metals or minerals are one of the suitable pharmaceutical forms in Rasashastra. Tamra Bhasma is one among them. Though wide utility of Tamra Bhasma has been mentioned in Rasa classics, Tamra is said to be a poison or more than a poison if used in Ashuddha (impure) form. There is a need to revalidate these classical principles and develop safety profiles to generate evidences. In this course, a screening has been done through the works carried out in the Department of RS and BK, IPGT and RA, Gujarat Ayurved University, Jamnagar. Twelve studies have been carried out in the department. Initial study was done by Prof. HS Sharma under the guidance of Prof. Vasudeva Mulasankara Dwivedi in 1958. This work is familiarly known as “Shulba Shastram,” a compilatory work including comprehensive information on Tamra from the classics of Rasashastra. Remaining 11 works were compiled in the current attempt.
Out of the twelve, five each studies are based on pharmacological and clinical trials and one is based on analytical study.
Pharmaceutical findings
Studies on evaluating the significance of Tamra Shodhana were reported that, more Putas are needed for the preparation of Ashodhita Tamra Bhasma in comparison to Shodhita Tamra Bhasma. Studies concluded that, Shodhana imparts increased brittleness, reduced hardness and particle size of Tamra.[25] Pharmaceutically, preparation of STB was found to be easier than preparation of Tamra Bhasma. Preparation of the product in EMF is reported to be convenient over Valuka Yantra posing to certain conveniences. Kramagni Paka for STB has been standardized in terms of time (of 12 h duration) and temperature (Mridu Agni – 120-250°C, Madhyama Agni – 250-450°C, and Tivra Agni – 450-630°C).[10]
Analytical findings
Initial studies reported the nature of Tamra Bhasma as copper sulfide,[8] while the Bhasma prepared in the presence of Rasa Bhasma was found to be cupric oxide in nature associated with 30 other associated elements.[23] Other studies identified Tamra Bhasma as copper oxide (CuO) along with copper manganese oxide (CuMn2O4) in minor phases. STB was reported to contain Cu, As, S, and Hg and is identified as Aktashite (Cu6Hg3As4S6).[22] AES-ICP revealed 56.42% copper and 23.06% sulfur in Tamra Bhasma prepared from Shodhita Tamra while Bhasma prepared from Ashodhita Tamra (99.9% pure copper) found to contain 44.91% copper and 45.35% sulfur. Traces of manganese, lead, arsenic, and zinc were found in both samples. Phase identification of Tamra Bhasma by X-ray diffraction revealed copper sulfate hydroxide [Cu4SO4(OH)6] and copper sulfide (CuS) in both samples of Bhasma, respectively.[26] All these studies, reveal that Bhasmas prepared in different media have different compositions and show different chemical reactions. This gives an idea that specific clinical efficacy of a particular Bhasma incinerated in specific media may be due to its specific chemical composition and trace elements present in it.
Pharmacological findings
No mortality with Tamra Bhasma was reported in acute toxicity at 30 TED[22] and 180 TED levels.[26] Sub-chronic toxicity studies evaluated the safety of Tamra Bhasma at five TED levels,[23] while chronic toxicity studies reported mild fatty degenerative changes in visceral organs with 5 TED. STB was reported to be safe, and no mortality was reported in acute toxicity at 30 TED.[22] Further studies attempted on evaluating the impact of Shodhana procedure. Tamra Bhasma prepared from Shodhita Tamra was reported to be safe in the sub-chronic study. In contrast, Bhasma prepared from Ashodhita Tamra was found to be toxic even at TED levels.[26] Significant anti-hyperlipidemic and cardio-protective activities of STB in comparison to Tamra Bhasma in experimental studies were reported.[22] Later studies also reported similar findings with Tamra Bhasma prepared from Shodhita Tamra, which was absent in Bhasma prepared with Ashodhita Tamra.[26]
Clinical findings
Therapeutic efficacy of Tamra Bhasma has been validated in cases such as Shvasa, Amlapitta, Kasa, Yakrit-Pliha Vriddhi, and Grahani Roga. In all the studies, the Bhasmas were administered by mixing with suitable herbal powders and adjuvants. The therapeutic dose was ranging in between 65 and 250 mg. On comparison, the effect of STB is reported to be more significant than the Tamra Bhasma. No adverse effects were reported in any of the clinical studies.
Conclusion
Metals and minerals are the integral parts of therapeutics in Ayurveda. Tamra, one of such metals been advocated in different forms in the management of various diseases. Classical texts emphasized on following classical guidelines (such as Shodhana and Marana) while preparing Bhasmas (incinerated powders) of the metals. This applies to Tamra too. Impact of Shodhana has been proven in studies which reported that Ashodhita Tamra poses inconvenience at pharmaceutical, pharmacological levels and proven to be toxic at TED level.
Analytically Tamra Bhasma is reported to be either sulfide or oxide of copper. The differences in chemical forms of incinerated copper reveal that Bhasmas prepared in different media have different compositions and show different chemical reactions. Pharmacologically, mild degenerative changes in visceral organs were observed in acute, sub-chronic, and chronic toxicity studies at higher dose levels. It implies that properly prepared Tamra Bhasma is safe to be used under the supervision. The samples were proven to be potent anti-hyperlipidemic and cardio-protective agent.
The clinical efficacy of Tamra Bhasma has been studied in Shvasa, Kasa, Yakrit Pliha Vriddhi, Grahani, etc., The dose of Tamra Bhasma administered was ranging from 65 to 250 mg, and the duration was up to 45 days. The Bhasma was administered along with various suitable herbal powders and adjuvants like honey. Positive results with a decrease in the intensity of signs and symptoms were reported in all the studies. These studies were limited to a few number of cases, hence statistical significance did not draw. Since no adverse effects were reported in any of these studies, and satisfactory responses were noted by the patients; the results can be considered as a lead for further well stratified studies covering larger population. In all aspects, (pharmaceutical, pharmacological, and clinical) STB is reported to be better than Tamra Bhasma. All these studies prove that, the classical principles have their own scientific rationale and need to be followed mandatorily while processing in order to avoid the possibilities of unwanted effects.
Acknowledgments
Authors duly acknowledge all the scholars and involved technical authority, whose works have been screened in the current attempt.
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