Module on “Ayurveda and Drug Re-purposing” by Dr. Prashant Gupta

Understanding of Drug repurposing in Ayurveda

Content 

In past decade, it is felt that drug discovery is time consuming (large gestation) and an uncertain million dollar affair. The process from a compound to drug almost take 15 years and at least 2 billion dollars are required to transform a compound in to a drug. Denovo drug delivery process has a high attrition rate precisely in a 1 million screened compounds only I reaches to clinical uses showing tract attrition.

Now, a clinical phases faces significant ethical issues and stricter norms, intact getting regulatory clearance from the central govt or state Govts is difficult. It is a marathon.

Hence considering all this scientist are now moving to more pragmatic approach for drug discovery and they are –

• Drug repurposing
• Reverse pharmacology

Today , we will only discuss drug repurposing

Definitions –

Drug repurposing – Identifying , developing and commercialising new uses for existing or abandon drug. Eg. Hydroxychloroquine

Drug Repositioning – Finding new uses outside the scope of original medical indication for existing drug.

Drug Reprofiling – Reducing the risk and cost associated with drug development with the advantage that the drug has already undergone a pre clinic and clinical testing. Eg. Thelidomide uses for Nausea in 1950s and for Leprosy in 1980s.

Drug Rediscovery – Investigating new uses for currently prescribed drugs.

Drug reformulation – Finding ways to modify a formulation to allow a drug to enter a new market/therapeutics. Eg. Triphala and Balachaturbhadra.

Therapeutic Switching – Opening up a new possibility for a old medicine that were not appreciated at the time of original discovery and can be therapeutically different through new formulations.

Indication Switching – Exploiting established drugs that have already been approved for treatment.

Need of the repurposing –

– Gestational time of de novo drug discovery

• Success Rate
• Cost
• Data Availability

How Drug Repurposing is designed –

• Machine Learning
• Network Analysis
• Analysis of omic data

Let us discuss the few points regarding drug repurposing

• Drug-Drug Similarity — Chemical Structure, targets, side effect, gene ontology
• Disease-Disease Similarity — Phenotype , Human phenotype ontology, gene ontology.

Indian traditional Medicine was a geographically influenced/dominated health management system of south east Asia. Time to time it incorporated/ adopted the prevailing science of era for health management viz. Herbominerals  and metal bhasmas during renaissance of alchemy proving its development has spatiotemporal contribution.

Ayurveda concepts of repurposing , therapeutic switching, new indication, drug reprofiling, therapeutic potentiation or near terms may be seen scattered in classics.

Why it was need during ancient time –

• Geographical limitations of drug availability.
• Seasonal Limitation
• Environmentally very concerned
• Storage and transport

Ancient Tricks of Drug Repurposing –

• Anupaan
• Yukti
• Kalpana
• Bhavana
• Sewan Kaal
• Maatra

These six tricks (which I thought) were traditional repurposing techniques for utilising the available drugs to the disease prevailing.

Three types of Treatment in Ayurveda

• Dosha pratyanik
• Vyadhi Pratyanik
• Ubhaya pratyanika

Questions:

1. Give two examples of Anupana which change the indication of used drug.
2. Give example of some other drug which is indicated in different diseases at different doses.
3. Give two other examples of Bhavana.
4. Which of the following is not the prophylactic/therapeutic indication of Hydrocholoroquinone
   1. Malaria
   2. Rheumatoid arthritis
   3. Covid-19
   4. None

1. What do you understand about gene ontology?
2. What was the thought behind the pious collection of drugs in ancient time?
3. Write two methods to reduce the cost of drug development research.
4. Which of the following is the treatment method described in Ayurveda
   1. Dosha pratyanika chikitsa
   2. Vyadhi pratyanika chikitsa
   3. Ubhya pratyanika chikitsa
   4. All of above

1. Write two more traditional techniques of drug repurposing.
2. Ayurvedic drugs act through which of the following principle
   1. Rasa & guna
   2. Virya & vipaka
   3. Prabhava
   4. All of above

For further reading:

Acharya Priyavrat Sharma, Dravyaguna vigyan part I & II

Charak Samhita, purvardha & Utarardha

Sharangdhar Samhita, Madhyam Khand.

Bhav Prakash Nighantu

Drug repurposing ; a promising tool to accelerate the drug discovery process; drug discovery today; vol. 24 (10)  https://doi.org/10.1016/j.drudis.2019.06.014

An update on drug repurposing: rewritten saga of the drugs fate; Biomedicine and pharmacotherapy; Vol 110; https://doi.org/10.1016/j.biopha.2018.11.127