Preclinical and Clinical efficacy of Siddha drug Karisalankanni Chooranam in the management of Pandu noi (Iron Deficiency Anaemia)

Dr.K.Karpagavalli*, Dr.V.Rani**, Dr.T.Swathini*, Dr.K.HinaFirdouse***

*PG Scholars, Department of KuzanthaiMaruthuvam, Government Siddha Medical College, Arumbakkam

**Head of the department, Department of KuzanthaiMaruthuvam, Government Siddha Medical College, Arumbakkam

***PG Scholar, Department of NoiNaadal, Government Siddha Medical College, Palayamkotttai

ABSTRACT:

Siddha system is said to be one among the Indian system of medicines which deals with Five Boodhas and Three Humours in the diagnosing and treatment aspect of a disease. Siddhars classified diseases as 4448 types. PaanduNoi is one among them. Paandunoi symptoms are more or less equivalent to Iron deficiency anaemia. Iron Deficiency Anaemia (IDA) is a very common disease prevalent in the society. Long term oral iron therapy is commonly used as first line therapy but iron salts such as ferrous sulphate are associated with a high incidence of gastrointestinal side effects such as nausea, vomiting, diarrhoea or constipation. Because of their adverse effects, a safe, effective, cheap, and easily available drug is needed. Many drugs are available in Siddha system of medicine which have remarkable effects in treating anaemia. One such medicine is Karisalankannichooranam is indicated for anaemia mentioned in Siddha classical literature.

With the aim of that, this Poly Herbal preparation may be effective to manage childhood IDA without any synergistic effects. The present study was carried out to study the efficacy and safety of the Siddha poly herbal compound drug karisalankannichooranam with the application of modern parameters. The Karisalankannichooranam reveal no toxicity in the preclinical studies and hence proven to be safe for human administration.

From the pre- clinical pharmacological study it is evident that the trial medicine has significant Haematinic action. Also Karisalankannichooranam has been proved clinically. Since as it raises the haemoglobin level in a marked level to the patients given regularly for not less than 30 days along with supplementary diets. Both symptomatic and qualitative improvement were absorbed. For prognosis, routine haematological investigation was taken. During the treatment no adverse events were observed. Statistically it has been proved that it shows significant raise in the haemoglobin level.

KEYWORDS:

Paandunoi, Iron deficiency anaemia, Karisalankannichooranam, Balavagadam

BACKGROUND:

Siddha system is said to be one among the Indian system of medicines, i.e., it is one in the AYUSH group.Siddhars are those who lived and maintained their body as they desired best.There are various principles present in Siddha system said by different Siddhars. The major and common concept of Siddha deals with Five Boodhas and Three Humours, respectively Prithivi, Appu, Theyu, Vaayu, Aagayam along with Vatham, Pitham and Kapham.

The physiology, pathology, diagnosis and treatment in siddha is based on the above said three humours. When these Humours in the human body get affected, it is said to be Dhosha or kutram. The fluctuations of these humours leads to disease, the repair of these kutrams is the treatment procedure in Siddha.

Our Siddhars, not only concentrated on the diagnosis and treatment, they have followed and given a various principles to lead a healthy and hygienic life. Siddha is built by vast number of Siddhars, such as Navanadhasiddhar, padhinensiddhar, navakodisiddhar, navasiddhar. In this, padhinensiddhargal plays a major role in the Siddha system.

Agathiyar is said to be the first siddhar in padhinensidhargal. He have described that there are 4448 diseases in his book Agathiyarrathnachurukkanaadi. It includes 62 types of diseases and its classifications. According to this, Paandunoi is classified into 10 types.

Paandunoi symptoms are more or less equivalent to Iron deficiency anaemia. Iron Deficiency Anaemia (IDA) is a very common disease prevalent in the society. Long term oral iron therapy is commonly used as first line therapy but iron salts such as ferrous sulphate are associated with a high incidence of gastrointestinal side effects such as nausea, vomiting, diarrhoea or constipation. Because of their adverse effects, a safe, effective, cheap, and easily available drug is needed. Many drugs are available in Siddha system of medicine which have remarkable effects in treating anaemia. One such medicine is Karisalankannichooranam,which is indicated for anaemia in Siddha classical literature.

With the aim of that, this Poly Herbal preparation may be effective to manage childhood IDA without any synergistic effects. The present study was carried out to study the efficacy and safety of the Siddha poly herbal compound drug karisalankannichooranam with the application of modern parameters.

OBJECTIVE:

To evaluate the efficacy of Herbal Formulationkarisalankannichooranam in the treatment of iron deficiency anaemia(IDA).

MATERIALS AND METHODS:

STUDY DESIGN:

An open clinical trial on paandunoi was carried out in the OP of P.G KuzhanthaiMaruthuvam Department attached to Aringnar Anna Hospital of Indian Medicine, Chennai-106.

The study was approved by Institutional Ethical Committee(IEC) and approval number is GSMC-CH-ME-2/01/20182017

POPULATION AND SAMPLE:

The population consists of all patients satisfying the inclusion and exclusion criteria mentioned below. Sample consists of paandunoi patients who were attending the OP of Aringnar Anna Hospital, Arumbakkam, Chennai- 106.

SAMPLE SIZE:

The study is considered in 40 selected patients of both genders between age groups of 3-12 years.

INCLUSION CRITERIA:

Ø Age: 3-12 years

Ø Hb level between 7-12 gms

Ø Worm infestation

Ø Angular stomatitis

Ø Pallor of the skin, mucous membrane, nail bed and conjunctiva.

Ø Lack of concentration and poor school performance

Ø Fatigue

Ø Constipation

EXCLUSION CRITERIA:

Ø Known H/O of Metabolic disorder

Ø Known H/O of Haemolytic anaemia

Ø Patient with previous blood transfusion

Ø Patient with any other serious illness.

WITHDRAWAL CRITERIA:

Ø Exacerbation of symptoms.

Ø The subject develops adverse drug reactions and adverse event they will be withdrawn from the trial.

Ø Patient turned unwilling to continue in the course of clinical trial.

EVALUATION OF CLINICAL PARAMETERS:

Patients are clinically evaluated by using the following parameters

a. History taking:

Age, occupation, Socio economic status, complaints and duration, past illness, family history, and personal habits were recorded in the case sheets for every patients during his / her first visit to OP.

b. INVESTIGATIONS:

Blood : TC, DC, ESR, Hb

Urine : Albumin, Sugar,Deposit

c. SPECIFIC IVESTIGATIONS:

Blood : PCV, MCV, MCH, MCHC, Total RBC

Motion: Ova, Cyst, Occult blood

d. CLINICAL DIAGNOSIS BASED ON SIDDHA SYSTEM:

The parameters used to diagnose the disease paanduNoi in siddha system are as follows,

· Poriyalaridhal- Examination of five sensory organs – (AIYMPORI): Skin, Tongue and buccal cavity, Eyes, Nose and Ear (MEI, VAI, KANN, MOOKU and SEVI)

· Pulanaalaridhal- Examination by physical perception – (IYMPULAN): Taste, Vision, Tactile sensation, Sound and Smell.

· Vinaadhal- Examination by interrogation, which includes history of illness, examination by the physician by using his organs of sensory perception.

• Uyirthathukkal–Examination of Physical constituents of body

· Udalthadhukkal- Examination of body tissues

· Envagaithervu - Eight basic diagnostic parameters namely Naadi (pulse), Sparism (Touch), Naa (Tongue), Niram (colour), Mozhi (speech), Vizhi (Vision), Malam (Motion) and Moothiram (Urine)

STATISTICAL ANALYSIS:

Data analysis will be done in Microsoft excel 2013 and SPSS software.

QUALITY ASSURANCE:

The quality of the study will be assured as the whole study will be conducted in supervision of faculties of the department and guide of the study.

ETHICAL CONSIDERATIONS:

No ethics were violated during the study as the participants were included only after explaining the need of study and study procedure. Study was conducted only after getting official consent/Assent obtained. Confidentiality was maintained throughout the study.

STUDY INTERVENTION:

KARISALANKANNI CHOORANAM

DOSE: 200mg – 500mg twice a day dispensed in dry and clean pet bottles.

ADJUVANT: Honey

DURATION: 28 days

INGREDIENTS&QUANTITY: (1 thola = 10 gms)

The medicine was prepared after getting authentication from the Head of the department of Department of Bio-chemistry and the medicine was prepared under the guidance of staffs of Department of Gunapadam at the laboratory of Gunapadam, Government Siddha Medical College and Hospital, Palayamkottai.

PRE CLINICAL SCREENINGS:

Biochemical Analysis:

Qualitative Analysis of the trial drug revealed the presence of iron, chloride, calcium, starch, reducing sugar.

Phytochemical Analysis:

The phytochemical analysis of the trial drug shows that the drug contains Glycosides, Carbohydrates, Coumarins, Phenols.

Physico chemical Analysis:

Loss on drying at 105⁰C - 2.43%

Total ash - 17.6%

PH - 5

Acid insoluble ash - 0.26%

Water soluble extractive - 26%

Alcohol soluble extractive - 12%

TOXICITY STUDY OF THE DRUG:

IAEC NO: LV/11/CLBMCP/2018

Acute toxicity:

Acute and sub acute toxicity studies were conducted on experimental rats at C.L.BaidMetha College of Pharmacy, Chennai, Tamilnadu.

Acute toxicity study of the drug k was carried out as the OECD guideline-423 (Organisation to Econamic Co-operation and Development).

The acute toxicity study of my trial drug was studied and the drug was proved safer for long term administration, as it did not exhibit any significant toxicity at 2000 mg / kg body weight.

Sub acute toxicity:

Sub acute toxicity study as per the guideline of – 407. Under the dosage of trial drug 200mg / kg (Low dose), 400mg / kg (High dose) it did not exhibit any significant.

Histo pathology:

At the end of toxicity studies the animal were sacrified and they were subjected to hematological parameters (TC, DC &Hb) chemical parameters ( LFT, RFT) and histopathology of vital organs like Liver, Kidney, Spleen, Lungs were carried out. The studied did not exhibit the evidence of remarkable pathological lesions in the tissues.

Pharmacological activity:

The pharmacological studies of trial medicine Karisalankannichooranam showed significant Haematinic action wistar albino rats.

Haematinic action of Karisalankannichooranamwas carried out by producing anemia by administrating a single intramuscular injection ofdesferrioxamine at a dose of 15mg/kg b.w. Drop out period of four days was awaited until the sufficient drop in Hb level was noticed in animals. Rats were considered as anaemic model if haemoglobin concentration was less than 14g/dl. Then the trial drug was administered show a potent haematinic action during the studies.

RESULTS:

· Mean value of HB before treatment: 11.5 ± 1.57

· Mean value of Hb after treatment 12.01 ± 1.03

To analyse the significance, Paired T- Test is chosen

· Null Hypothesis: There is no difference between means

· Alternate Hypothesis: There is absolute difference between two means

P- Value= 0.04

· If the P-Value is less than 0.05, then the null hypothesis is rejected

· As the P-Value of this study is 0.04, Null Hypothesis is rejected and Alternate hypothesis is accepted. Thus concluding that there is difference in the means of before and after treatment.

· To signify the difference, Pearson correlation between two variables taken which shows the result of 0.87 (87%)

· As the r value of this study is 0.87, it shows that the result has Strong Positive correlation

· i.e statistical correlation is measured by what is called the coefficient of correlation (r). Its numerical value ranges from +1.0 to -1.0. It gives us an indication of both the strength and direction of the relationship between variables.

AGE WISE MEAN DIFFERENCE BEFORE AND AFTER TREATMENT:

MEAN DIFFERENCE BY SEX BEFORE AND AFTER TREATMENT:

SUMMARY:

To study the efficacy of Siddha trail drug Karisalankannichooranam as internal medicine for the treatment of PaanduNoi in children.This disease mostly resembles Iron deficiency anaemia in modern system. Literature evidences of both Siddha and Modern system were collected and also the ingredients of the trial drug was reviewed as well. For the clinical study, 40 patients were selected based on protocol. This study is conducted after the drug being screened by the Screening committee and approved by the Institutional Ethical Committee (IEC) of Govt. siddha medical college Chennai.

Selected patients with PaanduNoi diagnosed clinically treated in outpatient department of Govt. siddha medical college attached with Arignar Anna Hospital of Indian Medicine, Chennai-106. They were undergone laboratory investigation and treated with trial drug, observed for clinical improvement and any adverse reaction.

Qualitative analysis of the Karisalankannichooranam presence of iron, calcium, starch, chloride and Reducing sugar. Phytochemical analysis of the trial drug shows that presence of Glycosides, carbohydrates, coumarins, phenol.

Physico chemical analysis of the trail drug shows the pH 5, Total ash value 17.6% shows the safe and effectiveness of the trial drug.

Toxicological studies shows that, it has no significant toxic effect. From the preclinical pharmacological study shows that the drug has got a significant haematinic activity.

Among the 40 patient’s good improvement was observed in 20 cases (50%), moderate improvement in 13 cases (32.5%) and mild improvement in 7 cases (17.5%).

CONCLUSION:

Paandunoi is mainly caused by the derangement of Pithamfollowed by vatham and kabam. The deranged kuttram is settled down by the kaippusuvai in the trial drug there by medicine act effective in cure the disease.

In physico chemical Analysis iron was found to be present as effective ingredients in treating anaemia.

The Karisalankannichooranam reveal no toxicity in the preclinical studies and hence proven to be safe for human administration.

From the pre- clinical pharmacological study it is evident that the trial medicine has significant Haematinic action.

Also Karisalankannichooranam has been proved clinically. Since as it raises the haemoglobin level in a marked level to the patients given regularly for not less than 30 days along with supplementary diets. Both symptomatic and qualitative improvement were absorbed. For prognosis, routine haematological investigation was taken. During the treatment no adverse events were observed. Statistically it has been proved that it shows significant raise in the haemoglobin level. Hence it is concluded that the trial drug Karisalankannichooranam will be a better drug that can be used in the treatment of PaanduNoi.

ACKNOWLEDGEMENT:

I would like to sincerely thank Dr.V.Rani M.D(s), Head of the department, Kuzanthaimaruthuvam, Government Siddha Medical College & Hospital, Chennai for allowed and guided me to do this clinical study.

I would also thank Dr.C.Shanmugapriya M.D(S) and other faculties in our department who helped me in this study.

I would like to thank noble solutions for helping me in Biochemical and Phytochemical analysis of my drug.

I wish to thank Dr.P.MuralidharanM.Pharm,Ph.d, C.L.BaidMehtha college of pharmacy, Thoraipakkam, Chennai, to do toxicity and activity study of my drug.

I wish to thank Dr.K.HinaFirdouse for helping me in statistical analysis.

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