INTRODUCTION:

Ayurveda is the oldest documented system of medicine in the world, which is now regaining its past fame through global acclamation. Study of classical literature and collection of relevant data in different fields of research will enrich existing knowledge of ayurveda.¹ Nanomedicines a novel and fascinating drug delivery system founds its origin in ayurveda. Metallic nanoparticulate drugs are successfully used in ayurveda. These medicines are used in the form of rasaushadhis called as bhasmas whose particle size ranges in the nanodimensions (5-50µm). Bhasmas are products of Indian classical alchemy which is a branch of rasashastra (ayurvedic pharmaceutics) dealing with the drugs of mineral origin, their varieties, characteristics, processing techniques, properties and their therapeutic uses.

Rasausadhi’s are appreciated for their smaller dosages, quick effectiveness and long durability. Rasausadhi’s are found very effective for the promotion of positive health and prevention of diseases when compared for treatment of chronic diseases Ayurveda system of medicines is superior to allopathic system.² The use of metallic and mineral drugs including Rasa that is 8th to 9th century A.D and onward. Although ayurvedic system is having very high potential to treat chronic and diverse diseases, it is neglected till date.

Allopathic system of medicines called modern medicines is very newer to world and prevalently utilized from a century. The simple reason is it quickly gives respite from ailments and treats a person. This system of medicines got its fame faster due to modern tools, techniques, statistical data and novel formulations, which brought about many diseases to standstill. In modern medicines synthetic replacement for natural drugs is done by various ways like combinational chemistry, serendipity, random screening etc. Due to ability of quick action and selectivity this system is mostly preferred.³

Nanomedicine is a branch that involves science and engineering technology in design, synthesis, and characterization of a medicinal product at nanoscale or one billionth of a meter. Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. Nanomedicine exploits the improved physical, chemical and biological properties of materials at the nanoscale and offers the potential to enable early detection, prevention, improved diagnosis and imaging, treatment of diseases.^4,5 Nanomedicines are of three types- diagnostic, therapeutic and regenerative. Nanotechnology combines different traditional sciences like chemistry, physics, materials science and biology, to bring together the required collective expertise needed to develop these novel technologies. Nanoparticle probes can endow imaging techniques with enhanced signal sensitivity, better spatial resolution and the ability to relay information on biological systems at molecular and cellular levels.⁶

Besides the amount of benefits of contemporary designed nanoparticles in medical specialty, there come some drawbacks conjointly that may adversely impact the surroundings, each inside the build and inside the natural scheme. Some current hypotheses suggest that some engineered nanoparticles may be more toxic (inflammatory) than other fine-sized particles of identical chemical composition. Different physicochemical properties of nanomedicines such as particle size distribution, highly reactive surfaces, electrostatics properties, surface area, general structure and aggregation may adversely affect physiological interactions between nanomedicines and target organs. Consequently it is very important to finely maintain these properties so as to extend safety of nanomaterials. These are areas that need attention in order to realize the full translational potential of modern nanomedicine. For nanotechnologies with clearly associated health risks, intelligent design of materials and devices is needed to derive the benefits of these new technologies while limiting adverse health impacts and a rational science-based approach is needed to minimize harm caused by these materials, while supporting continued study and appropriate industrial development.⁷

Coarse direction of ayurvedic treatment is judgement of cause of disease and irradicating it unconditionally, this in like manner reduces serendipity of raid or side effect to the patient and gives permanent relief non-native disease. The information of Ayurveda is again diffusing through its kin furthermore, over the whole globe, through headways in present day science and innovation utilizing quick correspondence frameworks. In any case, with this acknowledgment, an interest for ayurvedic items has expanded hugely. To adapt to this worldwide request, generation of drugs has expanded by a wide assortment of producers, some of whom still can't seem to adjust to appropriate rules for large scale manufacturing. This hole right now forestalls customary fruitful scientist, clinicians of ayurvedic rasashastra from passing on their science to the cutting edge GMP and strategy world.⁸

The non -appearance of the understanding of the differences and similarities between the condensation doctrines of these systems is the first obstruction resemble their sharply defined unclear reticent foreign them every second impediments in the discovery of plant based medicines.⁹

This study aims to accumulate into on the ripen age old description notice and basic principles of ayurveda this would on ice the changed scholars, researchers and practitioners to knock off less perception of customary systems of subvention solid of the commodities and worn out the challenge towards their global acceptance and harmonization of such traditional nanomedicines.

Diagram 1: Benefits of ayurvedic bhasmas.

Ayurvedic bhasmas:

'Bhasmas' are metal or metal oxide based drugs. Metal/ metal oxide in the field of medicine got the status during “Samhita” period in its sense. A complex and elaborate procedure for the preparation of bhasma was described by Nagarjun around 800 AD in Rasashastra. According to ayurvedic metallurgy, bhasma is product of herbo-metallic process and contains both metallic and herbal ingredients, they are basically calcined form of metals/minerals treated with herbs. This process is strictly followed till date¹⁰. Bhasmas are believed to be ancient part of India as nanomedicine and are more efficacious than any other healing system. This is because their nanosize particles being insoluble can absorb and enter into the blood stream and, are more biocompatible as compared to any chemically produced entity due to its size/ volume ratio. The size of nanoparticles lies between 1 and 100 nm at least in one dimension¹¹. Bhasmas as compared to their herbal drug counterparts are stable over a longer period of time, require lower dose, are easy to store and sustainable availability.

Preparation method of bhasmas relating to nanotechnology:

In Rasashastra, metals and minerals are subjected to different Samskara like Shodhana, marana, bhavana jarana etc. to beget the properties like ‘Alpa Matra Upyogitvad’ (effective in low dose, potent) and ‘Kshipram Aarogyam Daayitvad’ (fast acting) in them. Shodhana is a process of purification and detoxification by which physical and chemical Blemishes and toxic materials are eliminated or nullified after which the substances are made suitable for further proceedings. During shodhana process tension is increased in material due to heating which further get reduced by emediate cooling with liquid media, this repeated heating and cooling finally increases brittleness, reduced hardness and ultimately reduced particle size. In bhavana process material is rubbed in between mortar and pestle which increases stress on particles of materials and further reduces size of them. Metal gets oxidized during jarana process which involves heating of material in open air, due to oxidation melting point of the material further increases. The concept of incineration or Marana is responsible for numerous changes which transforms these materials to a magnificent medicine. marana is the process which brings the particle size into nanometer range which makes the metal into absorbable and assimilable form and repeated incineration of metal with suitable raw material change the inherent quality of the metal, which render them non-toxic and suitable for the treatment of chronic ailments.

In brief these probable changes can be enumerated as; Reduction in particle size. Conjugation of trace elements etc.^12,13,14

Significance of put paka and kupupakwa method on nanostructured nature of bhasmas:

Putpaka method:¹⁵

Bhasma is being prepared by subjecting minerals or metals to three main procedures (Shodhana, Bhavana and Marana) Bhasmas are prepared by putpaka method in which minerals and metals are converted into microfine form. Putpaka is the process that indicates quantum of heat required by rasadi dravyas viz minerals and metals for their proper paka or incineration (puta means a mode of heating) which converts the metal into suitable form to be assimilable into the body.

Putayantra in ancient heating device explained by almost all acharyas which is used for Marana/ incineration of different metals and minerals etc. this yantra consists of two earthen sharavas or pots which are kept upside down in the mouth of another two sharavas in contact with each other. dravyas used for marana is kept in between the gap of two sharavas or pots and sealed with the help of multani mitti. According to resendra chudamani more no of putas converts the material into more fine (sukshma) form in incorporates wonderful therapeutic properties in bhasmas. (Put paka) The properties of bhasma prepared through puta includes Curnatva- Breaking the material to a powdered state by providing external heat to the metal, Laghuta – Lightness, Apunarbhava – Unable to regain its original form, Gunadhikya - Potentiation, Agrata – Making the drugs to its best form, Anapsu Majjanam –The obtained bhasma will not sink in water, Rekhapurnata - Occupying the inter ridge spaces of the finger, Sighravyapti - Spreading and occupying very rapidly, Dipanam - Increasing the appetite.

Kupipakwa method:

In this strategy, Bhasma are formulated by subjecting metals (gold, silver, copper, and so on.) to four stage procedures (Shodhana, Kajjali arrangement, Bhavana and Kupipaka). After Shodhana, metals are allowed for amalgamation with mercury, and afterward purged sulphur is blended and triturated till dark, drab, fine and smooth mass is readied. This technique is called as Kajjali preparation. Arranged Kajjali is levigated by particular fluid media for certain period. It is permitted to complete dryness and filled in a glass bottle (Kachkupi) covered by 7 layers of mud spread material. Container is then subjected to sand shower (Valukayantra) for indirect and homogeneous warming for a specific period. In the wake of self- cooling, bottle is broken, sublimed item is collected from neck and Bhasma is gathered from the base of bottle and ground to powder form^16,17

Important uses of bhasmas:

Saptadhatu bhasmas (Seven metallic Bhasmas) namely Suwarna (Gold), Rajat (Silver), Tambra (Copper), Louha (Iron), Vanga (Tin), Naga (Lead) and Yashada (Zinc) bhasma are widely used for treatment in ayurveda. All Bhasma have some common properties such as Rasayana (immunomodulation and anti‑aging quality), Yogavahi (target drug delivery), Alpamatra (prescribed in minute doses i.e., 15–250 mg/day), Rasibhava (readily absorbable, adaptable, assimilable, and nontoxic), Shigravyapi (spreads quickly and fast acting), and Agnideepana (increases metabolism at cellular level and acts as catalyst) Bhasma can be employed for selective/targeted/controlled drug delivery as they are biocompatible, nontoxic, and nonantigenic in nature.¹⁸

Few more examples of frequently used Bhasma include: Mukta Shukti Bhasma (pearl‑oyster calx) at 22.52 ± 0.45 μm size in acidity, pyrexia, tuberculosis, cough, asthma, etc., and also to increase the bone mineral density; Mandura bhasma (iron calx) in microcytic anemia and hemolytic jaundice, Tamra bhasma (copper calx) as hepatoprotective and antioxidant, Yashad bhasma (Zinc calx) in myopia, diabetes, leucorrhea, etc.^19,20

Swarna bhasma:

Swarna bhasma (Incinerated gold) is Madhur (Sweet), Hrudya (Heart tonic), improves intellectual power, Rasayana (rejuvenator), and alleviates increased doshas and Anti Toxic effect. Pharmacological review of Swarna bhasma reveals that it possesses immune modulator, free radical scavenging activity, analgesic activity and anti-stress activity.²¹

Pharmacological review of Swarna bhasma reveals that it possesses immune modulator, free radical scavenging activity, analgesic activity and anti -stress activity. In elemental analysis of Swarna bhasma by EDAX it is observed that As and Nb in trace amount. However presence of other trace element is not observed.²²

Finding proofs for nanodimentions of bhasmas:

Brown et al (2007) in their study evaluated the physico-chemical characterization of Swarna bhasma by using Transmission electron microscopy (TEM) shown average particle size of SB was 57 nm. In this study, 40 Putas were applied for the preparation and different procedure was advocated. It might be possible that increase in number Putas (incineration procedure i.e. heat duration, temperature and grinding) increases he fineness of particles.²²

Ras-Sindoor22 (sublimed mercury compound) is contains mercury sulfide (crystalline; size, 25 - 50nm) associated with several organic macromolecules derived from plant extract used during processing of drug. Several macro/trace elements are also be present in different amounts, which were bio-available and responsible for adding to medicinal value of Ras-Sindoor.²³

S. K. Sing et al synthesized and characterized lead based Indian traditional drug- Naga bhasma and found that particle size of lead bhasma lies in nano range. (~60 nm). They have also used transmission electron microscope (TEM) Philips, CEM, CM-12 for characterization of nano structure of sample.²⁴

Finding proofs for safety of ayurvedic bhasmas:

Ayurvedic formulations containing heavy metals have been used since long duration with claimed viability and safety; however questions are frequently raised about toxicity due to heavy metals used in preparations.

Gajendra Kumar and Yogendra Kumar Gupta studied Evidence for safety of Ayurvedic herbal, herbo-metallic and Bhasma preparations on neurobehavioral activity and oxidative stress in rats, the results of their study were sound with the Ayurvedic literature. There were no significant changes in cognitive and motor functions and biochemical parameters of Calcury, Energic-31 and Basanta Kusumkara Rasa treated rats, demonstrates the safety of Ayurvedic formulations. These drugs are clinically used by a large number of populations without showing heavy metals toxicity. Hence, Calcury, Energic-31 and Basanta Kusumkara Rasa can be used at recommended dose and duration.²⁵

Swapnil Y. Chaudhar et al studied acut and subchronic study of tamra bhasma prepared with and without amritikaran and concluded that both the samples of tamra bhasma did not produce any sign and symptoms of toxicity at therapeutic dose level (5.5mg/kg) and therapeutic equivalent dose (TED) 5 (27.5mg/kg) while at higher dose of TED, 10 (55mg/kg), which are not likely to be ever employed in clinical conditions, has mild toxicity in liver, kidney, heart, and thymus on repeated administration for 28 days in rats. The sample without Amritikarana has more magnitude of toxicity than the sample with Amritikarana, this proves the importance of processing parameters of ayurveda on safety and efficacy of bhasmas.²⁶

Pallavi Shrirang Jamadagni et al carried out an experiment on toxicity studies of swarna bhasma, an ayurvedic medicine containing gold, in wistar rats and found that, Swarna Bhasma was safe up to dose rate of 13.5mg/kg/day when administered orally for 90 consecutive days in Wistar rats. The results of the study support the safety of Swarna Bhasma, which is being used traditionally since centuries without any adverse drug reactions. As per the Ayurvedic classical literature, detoxification procedures called “Shodhana” and “Marana” during drug preparation are responsible for decreasing the inherent toxic potential of gold and minerals used in Swarna Bhasma.²⁷

Bhasmas are produced by method of calcinations, calcinations brings about chemical change in a metal and converts a metal into its metal oxide. Transformation of metal into its oxide may lead to conversion of zero valent metal state into form with higher oxidation state and due to this conversion toxic nature of resulting metal oxide is completely destroyed while inducing medicinal properties into it.¹⁸

Amalgamation of modern techniques with ayurvedic bhasma:

Babita kale et al, synthesized vanga bhasma by two different methods –first is traditional heating method prescribed in ayurvedic literature and second –use of muffle furnace for heating, and the got significant difference in results. There studies revealed that Vanga Bhasma prepared by traditional method of heating has 50% nanoparticles (150–300nm range) that prepared by using electric muffle furnace has 100% nanoparticles (50–100nm range), this proves that if we can use modern heating method then time of heating is reduced with reduced particle size^.28

Accurate Standardization of bhasma is crucial step at present because bhasmas have good rejuvenating, curative and preventive potential for number of diseases. Bhasmas are good when prepared using proper procedure at the same time they can harm too if prepared in improper and short cutaways. There is need of systemic and well organized coordination between allied sciences along with modern methodologies and facilities to improve quality and safety profile of these wonderful medicines.

In classics different physical and chemical tests are utilized for standardization like varna (colour), varitara (float), rekhapurna (furrow filling), unama anjana sannibha (softness), nischandra (lusterless), sukshmatva (fineness), gutarasatva (tastelessness), apunarbhava (irreversibility), nirutha (irretrievable), amla pariksha (sour taste), aksharatwa (lack of alkaline taste), compliance of prepared bhasma with all these tests proves its proper formation. Modern techniques EDAX, SEM (chemical nature, size and morphology of particles), TEM, AFM (particle size, size distribution), EPMA (distribution of individual elements), XRD (phase analysis), XRF, PIXE (bulk chemical analysis after making pellets, detecting metal as elements), ECSA (electronic nature and oxidative state of metal), extraction and chromatography (to extract out organic matter if any) HPLC, MALDI, IR (characterization of organic matter) can be successfully combined with these traditional confirmatory tests to improve quality and acceptance of these bhasma preparation.⁴

CONCLUSION:

Bhasmas as nanomedicines may offer a huge potential for designing new drugs employing the concept of nanotechnology. The structure and effectiveness of the bhasmas as drugs depend largely on their processing history. bhasmas are generally safe drugs for human beings in spite of the presence of seemingly toxic elements and compounds as indicated by recent studies using modern analytical techniques. Thus, the standardization of fabrication process of these formulations is a crucial issue to be addressed. Neverthless, more systematic nanomaterialistic investigations on bhasmas are recommended for gaining the complete and reliable composition-processing–structure-effectiveness picture of these drugs. Currently there is an urgent need for the practitioners of modern and traditional systems to standardize the synthesis procedure, rigorous scientific analysis for the quality, safety of these metal-based bhasmas.

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Received on 11.06.2020 Modified on 29.07.2020

Asian J. Res. Pharm. Sci. 2021; 11(1):65-70.

DOI: 10.5958/2231-5659.2021.00011.4

Sr. No	Ayurvedic Bhasma	Ingredients	Uses
1	Vasant Kuskumar rasa	Gold, silver, coral	Complications of diabetes, neuropathy, general weakness
2	Tamra Bhasma	Copper, mercury, sulfu	Anemia, jaundice, digestive disturbance, abdominal disorders
3	Loha Bhasma	Iron, cinnabar	Enlargement of liver, anemia, jaundice
4	Abhrak Bhasma	Calcined purified mica ash	Respiratory disorders, diabetes, anemia, general weakness
5	Swarna Bhasma	Ash of gold (Calcined gold)	Improves body immunity, general weakness, anemia, energetic
6	Praval Panchamrit	Powder of corals, pearls, conch shells	Praval Panchamrit Richest source of natural calcium, agitation, acidity, burning sensation
7	Swarna basant malti ras	Gold, piper-nigrum, white pear powder	Tonsillitis, fevers, cough, bronchitis, decreased immunity, cancers, autoimmune disorders
8	Kamdudha ras	Ochre, Tinospora cordifolia, mica (calcined)	Hyperacidity, headache, fever, blood pressure

1. Chauhan A et al. Ayurvedic research and methodology: Present status and future strategies. Ayu. 2015; 36(4); 364–369.

1. Chauhan A et al.Ayurvedic research and methodology: Present status and future strategies.Ayu. 2015; 36(4); 364–369.