EFFICACY AND SAFETY OF HMS19, A SIDDHA POLYHERBAL DRUG IN  RESPIRATORY DISORDERS AND ITS SCOPE IN THE MANAGEMENT OF COVID19

Santhigiri Research Foundation | Santhigiri Healthcare & Research Organization

The COVID-19 pandemic has spread across the world and the reported cases in India is rapidly ­increasing, and is expected to peak during the coming months of August and September 2020. It is a National ­Emergency and need of the hour, for the rapid development and deployment of an ­effective ­therapeutic intervention to contain this epidemic.

In this scenario, India also has an opportunity to explore the vast repository of its traditional medicines as an effective intervention against COVID 19. Among the traditional medical systems in India, one of the oldest and most validated by use, is the Siddha System of Medicine. It is of tremendous importance at this juncture to note that, the manuscripts of this system, describes such outbreaks and management of such pandemic outbreaks during those days.

To combat the current health crisis, created by the Novel Corona Virus, the Siddha Doctors and ­­Scientific Fraternity of the Santhigiri Research Foundation, under the spiritual guidance of founder Guru of ­Santhigiri Ashram, has formulated a proprietary Siddha Medicine, based on proven and ­efficacious ­classical ­Siddha Formulations and designated as HMS19. We anticipate the medicine to have ­significant ­Antiviral, ­Anti-inflammatory and Immunomodulatory activities, along with its basic ­indications, which will be ­evaluated through this Pilot Study.

ABOUT THE MEDICINE

Form of Medicine        : Maṇappāku – Thick sweet syrup form

Composition of Medicine        : Justicia adhatoda, Vitex negundo, Glycyrrhiza glabra, Piper ­longum, ­Andrographis paniculata, Chrysopogon zizanioides, Plectranthus vettiveroides, Santalum ­album, Trichosanthes cucumerina, Cyperus rotundus, Zingiber officinale, Piper nigrum, Mollugo cerviana, Rock ­Sugar, Menthol, Camphor, Honey.

Usage Instructions

Dosage        :        10 – 15 mL

Adjuvant        :        twice as much tepid water

Indication(s)        :        Neñcaṭaippu (Chest Congestion), Mūkkaṭaippu (Nasal Congestion),
Kaphakkeṭṭu (Increased Phlegm Accumulation), Kapha Kāsam
(Cough due to Chest Congestion), Moorchiraippu (Dyspnoea), Suram
(Fever), Jaladōṣam (Rhinorrhoea), ­Tummal (Sneezing), Pīnasam
(Sinusitis), Thondaivali (Sore throat).

Justification of Ingredients

The Classical Siddha Formulation – Āṭātōṭai Maṇappāku, forms the basis for the proposed ­formulation – HMS19. Which is fortified with the ingredients from four other handpicked proven Classical Siddha ­Formulations viz. Nilavēmpu Kuṭinīr, Kapasura Kuṭinīr, Nocci Kuṭinīr and Āṭātōṭai Kuṭinīr. All these ­medicines are proven to have significant Antiviral, Antimicrobial, Antipyretic, Anti-inflammatoy, ­Analgesic and ­Immunomodulatory Potentials and those were validated clinically and experimentally, in the past.

• Āṭātōṭai Maṇappāku, yet another Siddha Classical Preparation, with the well known and lot studied leaves of Justicia adhatoda, as its active ingredient. Primarily, this drug has significant Expectorant, ­Decongestant and Antimicrobial potential [8, 7].
• During the year 2015, the Siddha had played a noteworthy role in containing the outbreak of the Chikungunya virus, in the state of Tamilnadu. Nilavēmpu Kuṭinīr, a Classical Siddha polyherbal ­medicine, was the ­elixir drug, that played the key role during that pandemic outbreak. The drug is proven to have ­significant ­Antiviral [1, 7][9, 7], Antimicrobial [2, 7][9, 7], Immunomodulatory [3, 7][9, 7], Antioxidant [4, 7] and ­Antiatherogenic ­potential [4, 7];
• Kapasura Kuṭinīr, a Siddha Classical medicine in decoction form, is now being employed as the ­potential drug, to contain the pandemic – COVID 19, in the State of Tamilnadu. The effectiveness of the medicine in the management of COVID 19 has been clinically evaluated by National Institute of Siddha, ­Chennai, Tamilnadu, in association with SRM Medical College [6, 7]. The ­decoction is proved to have ­significant ­Anti Inflammatory [5, 7], Antipyretic [5, 7] and Antibacterial ­Activity [5, 7]. Recently it has been validated that the phytoconstituents of Kapasura Kuṭinīr has inhibiting effect against spike proteins of SARS CoV 2 [10, 7].
• Nocci Kuṭinīr, is a widely used Siddha Medicine, against fever and chest infections. The ­phytochemical evaluation of the drug, has shown its significant Antioxidant [7, 7], Antimicrobial [7, 7], ­Anti-Inflammatory [7, 7], Antidiabetic [7, 7] and Antihypertensive potential [7, 7].
• Āṭātōṭai Kuṭinīr, is yet another classical and widely used Siddha Formulation, which is of ­significant ­importance in the management of many respiratory diseases including Allergic conditions and ­Asthma [11, 7].

Considering these proven potentials of the aforementioned classical Siddha medicines, Ministry of AYUSH has accorded the Nilavēmpu Kuṭinīr, Kapasura Kuṭinīr and Āṭātōṭai Maṇappāku as Siddha ­preventive and immuno-modulatory medicines in the prophylactic management of COVID 19.

PILOT STUDY

Considering the proven clinical efficacy and background research citations of the classical reference formulations, the new formulation – HMS19, will obviously carry similar therapeutic efficacy as a potent formulation for the said indications.

To substantiate this anticipation, and to evaluate the acute clinical efficacy of the drug, a pilot study has been carried out, at Santhigiri Siddha Medical College OPD and Santhigiri Ayurveda and Siddha Hospital, Kozhikode.

Objectives

1. Generate substantiating clinical and laboratory evidence for the anticipated acute therapeutic ­potentials of the new medicine – HMS19;
2. Generate substantiating laboratory evidence for the safety of the medicine;
3. Throw light on the anticipated Anti-inflammatory and Immunomodulatory potentials of the ­medicine, paving way for further studies on the medicine.

Study Design

Study protocol, evaluatory and assessment strategies were designed and appraised by the research ­committee of Santhigiri Research Foundation. The study was carried out with a total of 50 participants, selected at random, based on a simple selection ­criteria. All participants were given medication for 14 days. There blood and urine samples were taken for ­analysis before treatment, after 7 days of ­medication and at the end of medication.

Evaluation of Therapeutic Efficacy and Safety

Evaluation based on Clinical Findings

The Clinical Evaluation of the patients were conducted before medication, at the midway and at the end of the study for the therapeutic efficacy and safety of the drug, based on a preset Clinical Record Form.

A checklist of 17 chief respiratory complaints (Cough, Expectoration, Hemoptysis, Rhinorrhoea, NoseBleed, Sore Throat, Nasal Congestion, Chest Congestion, Dyspnoea, Chest Pain, Fever, Headache, Body

Pain, Fatigue, Chills, Allergic Signs/Symptoms), were evaluated during each assessment. Along with this, personnel and occupational history of the patient was taken to understand any sort of diseases or conditions which might be the predisposing factor and/or worsening factor for the presenting complaints.

Also the details on the ongoing medications, treatment or surgical history, relevant family history, details on other debilitating diseases like Diabetes mellitus, Hypertension, Cardiovascular illness etc. were taken.

The clinical assessment was followed by data cleaning and analysis. The symptom wise evaluation of the entire trial population is summarized and depicted in Chart 1.

Evaluation based on Laboratory Findings

The blood and urine samples of the patients were collected during each assessment and subjected to Laboratory Analysis based on the parameters specified in the Clinical Record Form. The laboratory evaluation was carried out to prove the safety and to generate data to substantiate the clinical ­efficacy of the drug.

STUDY OUTCOME

The entire study population (50) was divided into two groups, acute having 28 participants and chronic having 22 participants.

Efficacy Evaluation – Based on Clinical Findings

As mentioned earlier the entire study participants were divided into two groups – Acute and Chronic. The statistical analysis of the data, collected during the assessments, reveals that the medicine has greater potential in alleviating the signs and symptoms of Acute Respiratory Tract conditions, than in Chronic conditions where the response is marginally lower than in acute cases, which might be due to the short study period. The consolidated data is depicted in Charts 2 & 3.

Efficacy Evaluation  – Based on Investigational Findings

• Erythrocyte Sedimentation Rate is a classical and general marker of inflammation. Higher values of which signifies some sort of inflammation in the body. It has been found that at the end of the study period, the Erythrocyte Sedimentation Rates of a greater number of participants are decreased substantially.
• Platelet Count is found to be a significant haematological parameter that gets decreased significantly in viral infections.
  This is true in case of the current pandemic the COVID 19. It has been found that at the end of the study period, the platelet count of a great majority of the study participants has got a significant hike in its level.
• Differential and Absolute Eosinophil Counts are general markers of parasitic infection of any sort.
  They will also get increased in allergic conditions and in acute infections. With the administration of the study medicine, it has been found that, at the end of the study period, the Eosinophil counts declined substantially.
• C – Reactive Protein (CRP) is an important marker protein, synthesized by liver, in response to inflammations.
  Research report confirms that the level of CRP is significantly increased in COVID 19 patients. It has been found that at the end of the study period, the CRP of a great majority of the study participants shown a significant decrease in its level.
• Lactate Dehydrogenase (LDH) is an enzyme found in nearly all living cells, which catalyzes the conversion of Lactate to Pyruvate and back. It is expressed extensively in body tissues, such as blood cells and heart muscles. Thus a higher level of LDH signifies tissue damage/inflammation, especially, in common injuries and cardiac ailments like Myocardial Ischemia and COVID 19. With the administration of the study medicine, it has been found that, at the end of the study period, the LDH level declined substantially.

Safety Evaluation

Safety of the medicine has been evaluated based on the comparison of the observed values and inferences at the end of the study, with the baseline data of Complete Blood Count, Liver Function Tests, Kidney Function Tests, Serum Electrolytes and Basic Urinalysis.

All the parameters under these heads were analysed and no alarming changes were observed.

CONCLUSION

The results of the study shows that the new formulation has noteworthy potential to alleviate Chest Congestion, Nasal Congestion, Increased Phlegm Accumulation, Cough due to Chest Congestion, Fever, Rhinorrhoea, Sneezing, Sinusitis. The comparative analysis on the laboratory parameters reveals that the medicine is having significant Anti-inflammatory Potential and Immunomodulatory potential.

Being a short term study aimed at generating evidence for the acute efficacy of the medicine, and to throw light on potentials of the drug, this won’t explore and conclude the therapeutic potentials of the medicine.

The results of the current study, on HMS19, laid a scope in prevention, mitigation of COVID19 (may be correlated to Kapa Suram) cases. However extensive preclinical and clinical evaluations are necessary to substantiate its multifaceted potential against SARS CoV 2 infection.

RESEARCH COORDINATORS

1. Dr. B. Rajkumar, Medical Superintendent, Santhigiri Healthcare & Research Organization
2. Prof. Dr. K. Jagannathan, Principal-in-Charge/Vice-Principal (Academic), Santhigiri Siddha ­Medical College

DATA COLLECTION, ANALYSIS & REPORT GENERATION

1. Dr. Shabel P. V., Additional Medical Officer, ­Santhigiri Healthcare & Research Organization
2. Dr. Rajesh R. R., Additional Medical Officer, ­Santhigiri Healthcare & Research Organization
3. Dr. Brahmadathan U., Deputy Medical Officer ­(Production – Siddha), Santhigiri Ayurveda & ­Siddha Vaidyasala
4. Dr. Aneesh S. Murukan, Assistant Medical ­Officer (Siddha), Santhigiri Healthcare & Research ­Organization
5. Dr. Narayana Prasad R., Assistant Medical ­Officer (Ayurveda), Santhigiri Healthcare & Research ­Organization

ACKNOWLEDGMENT

1. Dr. Rajmohan, DGM (HCS), HindLabs, HLL Lifecare Limited, Thiruvananthapuram
2. Dr. P. Hariharan, Vice-Principal (Clinical), Santhigiri Siddha Medical College
3. Sri. Vijayan, Assistant General Manager (Administration), Medical Education Division, Santhigiri Healthcare & Research Organization

REFERENCES

1. Jaspreet Jain, Ankit Kumar, Vimal Narayanan, R.S. Ramaswamy, P. Sathiyarajeswaran, M. S. Shree Devi, M. Kannan, ­Sujatha Sunil (2018) Antiviral activity of ethanolic extract of Nilavembu Kudineer against Dengue and Chikungunya virus through in vitro evaluation. Journal of Ayurveda and Integrative Medicine: page 1 – 7;
2. Sujeethasai Krishna, Thayalini Thileepan (2018) A Review on Pharmacological activity of Nilavembu Decoction used in Suram (Fever). Journal of Research in Traditional Medicine: Page 83-86;
3. R Kavinilavan, P Mekala, M J Raja, M Arthanari Eswaran and G Thirumalaisamy (2017) Exploration of ­Immunomodulatory Effect of Nilavembu Kudineer Chooranam against Newcastle Disease Virus in Backyard Chicken. Journal of ­Pharmacognosy and Phytochemistry: Page 749-751;
4. Perumal Rajalakshmi, Vellingiri Vadivel, Sridharan Sriram, Pemaiah Brindha (2020) Evaluation of in vitro antioxidant and anti-atherogenic properties of selected Siddha polyherbal decoctions. International Journal of Research in ­Pharmaceutical Sciences: Page 1707 – 1715;
5. Saravanan J, Neethu Devasia, Gopalasatheeskumar K, Sanish Devan V, Thanga Kokila K and Sanjay M (2018) ­Anti-Inflammatory, Antipyretic & Antibacterial Study of Kabasura Kudineer. International Journal of Current Advanced Research: Page 9992 – 9997;
6. 13 COVID19 patients were ­admitted in SRM Medical College and Hospital, Chennai and successfully treated in ­association with National Institute of Siddha, Arumbakkam, Chennai. These COVID19 patients were treated with Kapasura Kuṭinīr along with allopathic medicine as integrative management (https://nischennai.org/nis-covid19-success-with-integrative-medicine-srm-may-2020.html);
7. G. Lalithambigai, M. Sakthiganapthi, G. Prakash Yoganandam, V. Gopal (2017) Pharmacognostical Standardization, GC – MS Analysis and In Vitro Screening of An Official Siddha Formulation – ‘Nochi Kudineer’. International Journal of ­Experimental Pharmacology: P 43-46;
8. Alka Sharma, Ashwani Kumar (2016) Antimicrobial Activity of Justicia adhatoda. World Journal of Pharmaceutical ­Research: P 1332 – 1341;
9. Jagannathan.K, Mohanambigai.G, (2020), Nilavembu kudineer, evidence based Siddha anti-viral and immunomodulating drug- a review, International Journal of Pharmacy and Biological Sciences, 10(2), 215-221;
10. Gangarapu Kiran et al, (2020), In-silico computational screening of Kabasura kudineer-official Siddha formulation and JACOM against SAR-CoV-2 spike protein, Journal of Ayurveda and Integrative Medicine (May);
11. Atul Kumar Gangwar and Ashoke K Gosh(2014), Medicinal uses and pharmacological activity of Adhatoda vasica, International Journal of herbal medicine, 2(1), 88-91.