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Journal of Drug Delivery and Therapeutics

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Clinical study to Evaluate Safety and Efficacy of Boozidaan (Pyrethrum indicum) in the management of Niqris Muzmin (Chronic Gout)

Josee Amin 1*, Dr. Naquibul Islam 2, Towseef Amin Rafeeqi 3

1. P.G. Scholar. Department of Moalijat, Regional Research Institute of Unani Medicine Naseem Bagh Campus, University of Kashmir, Srinagar, J&K, India

2. Professor, Department of Mo‘ālajāt, Regional Research Institute of Unani Medicine,S rinagar, J&K, India

3. Research officer, Biochemistry, Regional Research Institute of Unani Medicine, Srinagar, J&K, India

Article Info:

_________________________________________________

Article History:

Received 06 Jan 2024  

Reviewed 04 Feb 2024  

Accepted 21 Feb 2024  

Published 15 March 2024  

_________________________________________________

Cite this article as: 

Amin J, Islam N, Rafeeqi TA, Clinical study to Evaluate Safety and Efficacy of Boozidaan (Pyrethrum indicum) in the management of Niqris Muzmin (Chronic Gout), Journal of Drug Delivery and Therapeutics. 2024; 14(3):8-21

DOI: http://dx.doi.org/10.22270/jddt.v14i3.6447       _________________________________________________

*Address for Correspondence:  

Josee Amin, P.G. Scholar. Department of Moalijat, Regional Research Institute of Unani Medicine Naseem Bagh Campus, University of Kashmir, Srinagar, J&K,190001, India

Abstract

____________________________________________________________________________________________________________

Objectives: The objectives of this study were to observe the Efficacy of unani pharmacopoeial formulation Boozidan (Pyrethrum indicum) for the management of Niqris Muzmin (Chronic gout) and to observe any concomitant and adverse effects of formulation.

Methods: This single blind, randomized and standard control clinical study was conducted between April 2021 to October 2021 for a period of 28 days. 60 patients diagnosed with chronic gout were divided into two groups, 30 Test group and 30 Control group. The test group was administered with 5g boozidaan in powder form once daily with water and the patients of control group were given tablet febuxostat 80mg once daily. Patients were followed up and improvements in subjective parameters were assessed weekly at 7th, 14th, 21st, and 29th day. Objective parameters were assessed at the baseline and at 29th day. The data obtained was subjected to statistical analysis. 

Results: Both the test and control drug were effective in reducing Serum uric acid level, ESR and CRP levels.  A significant improvement in subjective and objective parameters was observed in both test and control groups and no adverse effects were observed during and after the study.

However, the test drug had superior efficacy in reducing the objective parameters and it was statistically significant (p-value<0.0001). 

Conclusion: Both Boozidaan and Febuxostat were safe and significantly effective in resolving the symptoms and signs of gouty arthritis and both have significant effect on reducing serum uric acid level.

Keywords: Boozidaan, Chronic gout, Niqris, Febuxostat, serum uric acid, unani medicine

 


 

1. INTRODUCTION

Niqris (Gout) is the most common inflammatory arthritis in men and in older women. It is caused by the deposition of monosodium urate monohydrate crystals in joint fluid, bones, cartilages, tendons, bursa and other tissues secondary to hyperuricemia 1,2,3,4, 5, 6. Elevation of serum uric acid level (SU) or hyperuricemia is an essential prerequisite for the development of gout. As SU level exceeds the physiological saturation threshold of 6.8 mg/dl, urate can crystallize as MSU in and around joints2, 7, 8, 9. The cardinal feature and prerequisite for gout is defined as a plasma urate level >7mg/dl in males and >6 mg/dl in females2.

It is a chronic rheumatic illness characterized by very painful recurrent acute attacks of monoarthritis which affects metatarsophalangeal joints (MTP) in over 50% of cases. Other common sites are the ankle, midfoot, knee, small joints of hand, wrist and elbow. The axial skeleton and large proximal joints are rarely involved1, 7, 10. The clinical picture of gout is divided into asymptomatic hyperuricemia, acute gouty arthritis, intercritical period and chronic topheceous gout11.

Gout is the most prevalent arthritis in adults and its public health burden is increasing globally8. The prevalence of gout ranges from 1-4 % worldwide and its incidence ranges from 0.1 – 0.3%worldwide. Gout is more common in men than women by 3:1 to 10:112. It is rare in children and premenopausal females and its mean age of onset is 40- 50 years, in women the age of incidence is post menopausal2, 6, 13.

Annual incidence of gout is 2.68 per 1000 persons and its incidence increases globally due to poor dietary habits such as fast food, lack of exercise, increased incidence of obesity, metabolic syndrome11.

Risk factors of gout include excessive alcohol intake, excess consumption of purine rich diet (meat, seafood, sweetened beverages), surgery, trauma, sepsis, stress, starvation, dehydration, drugs like diuretics, pyrizinamide, cyclosporine, salicylates and lead toxicity. Systemic conditions associated with high risk of gout include cardiovascular diseases (CVS), poor renal function, Diabetes mellitus (DM), menopause, psoriasis, myeloproliferative disorders and genetic factors1,2,3,11,12 ,14,15,16. Gout has an strong impact on individual health and health care system 17 and is associated with functional impairment and diminished health related quality of life18. Patients with hyperuricemia or gout are at increased risk of developing a variety of comorbidities such as hypertension, CVS disease, DM, metabolic syndrome, chronic kidney disease and neurological disorders14, 16, 19, 20. Moreover, Gout is associated with excess mortality due to CVS causes17. Differential diagnosis of gouty arthritis includes septic arthritis, psoriatic arthritis, reactive arthritis, osteoarthritis, pseudo gout and rheumatism1, 2. Gout is mainly diagnosed by identification of the pathogonomic MSU crystals by joint fluid aspiration or in tophi aspirate11. Diagnosis is based on laboratory and radiological features. The gold standard of diagnosis is identification of characteristic MSU crystal in the synovial fluid using polarized light microscopy.

Management of gout is directed towards the treatment of acute gout, prevention of further attacks, identification and correction of factors that contribute to the disease2, 21. Weight reduction and reduction of urate concentration by low purine diet should be considered in the long-term management of gout2. Management of gout includes both pharmacological and non pharmacological approaches. Pharmacological therapies focus on Urate Lowering Therapy (ULT) and anti-inflammatory drugs. Non pharmacological therapies focus on dietary and life style changes including weight loss and exercise3. Management of gout includes management of flares, chronic gout and prevention of flares as well as management of comorbidities9,11,15. Lowering (SU) levels below the deposition threshold either by dietary modification and using ULT is the main goal in the management of gout. This results in the dissolution of MSU crystals preventing further attacks11.

Various drugs like Colchicine, Non-steroidal anti-inflammatory drugs (NSAIDS), corticosteroids, Probenecid and Sulfinpyrazone, and synthesis inhibitors like Allopurinol and Febuxostat are used in the management of gout22, 23, 24. However these medications are associated with systemic side effects like vomiting, Gastro intestinal ( GI) bleeding, Hepato renal toxicity and Hypersensitivity25. The draw backs of all the above mentioned drugs call for the development of novel drugs with similar or better efficacy and lesser toxicity than presently available drugs.

In unani system of medicine Niqris (Gout) is being treated since greeco Arab periods, unani physicians claim to possess many safe and effective drugs for the management of Niqris (Gout) described in unani classical text books. In ancient unani literature there are description of many drugs (single and compound formulation) used to treat various types of arthritis including gout which include Ashwagandaha (Withania somnifera), Halaila Zard (Terminalia chebula), Gokharu (Tribulus terpyrethrumrestris), Suranjanshirin (Colchium autumnale), sibrsaqotri (Aloe Barbadensis and Boozidan (Pyrethrum indicum),.

In unani system of medicine, Suranjan (colchicumluteum) is the standard drug in the management of Niqris (Gout). According to classical unani literature Boozidan (pyrethrum indicum) holds functional approximity to suranjan (colchicumluteum) in its efficacy. Boozidan (pyrethrum indicum), having Analgesic and Anti-inflammatory action, detoxifies morbid humors from nerves and joints. That is why single unani drug Boozidan (pyrethrum indicum) has been selected and formulated in powder form for the treatment of Niqris (gout). The present study has been carried out just to evaluate the safety and efficacy of Boozidan (pyrethrum indicum) in the management o f Niqris (Gout).

2. MATERIALS AND METHODS

This clinical study was a single blind, randomized and standard control clinical study conducted on Sixty (60) patients to evaluate the Safety And Efficacy of Boozidaan (Pyrethrum Indicum) in the management of Niqris Muzmin (Chronic Gout) at the Regional Research Institute of Unani Medicine (RRIUM), Naseem Bagh, Srinagar J&K from April 2021 to October 2021. An inclusive protocol was framed and approval was obtained from the Institutional Ethics Committee of Regional Research Institute of Unani Medicine (RRIUM), Srinagar (IEC No: RRIUM/KU/2020-21/Tech./PB-375) dated 27.01.2021 and registered prospectively in Clinical Trials Registry (CTRI) India (CTRI/2021/03/032150).

The study started by enrolling patients from OPD/IPD of RRIUM Hospital. Every patient was questioned for detailed history of the disease. The patients were clinically examined and their hematological, biochemical and radiological investigations were carried out. Clinical symptoms, history and investigations were recorded on prescribed case report form designed for the study. A detailed history of development of present clinical symptoms like pain, joint stiffness, restriction of movements, swelling and tenderness was noted on the case report form. A thorough history of past illness regarding diabetes mellitus, hypertension, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, septic arthritis, trauma, sepsis and blood dyscrasias as well as a detailed personal history regarding excessive consumption of purine rich diet, sedentary lifestyle, excessive intercourse, alcohol consumption, drugs and smoking was taken and recorded on the case report form. A detailed occupational history, Social Status as well as family history of diabetes mellitus, hypertension, Rheumatoid arthritis and gout was also noted. Thorough general physical examination was carried out. Appearance, built, nutrition, pulse, blood pressure, respiratory rate, temperature, lymphaedenopathy, oedema, cyanosis, icterus, pallor, clubbing etc were keenly observed and recorded on the case report forms. Thorough systemic examination of respiratory system, gastro intestinal system, nervous system, cardiovascular system and urinary system was carried out to exclude the patients with severe ailments of any above mentioned systems. A thorough examination of musculoskeletal system was also carried out and recorded on case report forms. The joint involved were examined for signs of pain, swelling, erythema, tenderness, raised temperature, tophi as well as active and passive movements at the beginning of the study (0 day) and thereafter regularly during the follow up i.e. at 7th,14th day,21th and 29th day. Investigations like CBC (Hb%, TLC, DLC), ESR, LFT (Sr. Bilirubin, SGOT, SGPT, ALP), KFT (Blood Urea, Sr. Creatinine, Serum Uric Acid) and Blood Sugar (F) were performed to establish the safety & observe the effect of our drugs on renal function, liver function and blood sugar. C- reactive protein (CRP) (quantitative) and Rheumatoid Factor (qualitative) on 0th day were done to rule out the presence of rheumatoid disease.USG abdomen, Urine- routine (Microscopic) and X Ray of affected joint were also carried out on day 0th (Baseline) and day 29th (after completion of the therapy). Mijaz of each patient was assessed during clinical examination on the basis of ten parameters (Ajnās ‘Ashara) mentioned in Unani literature. Diagnosis of gout was based on classical signs and symptoms of Niqris muzmin (chronic Gout) with uric acid level >7mg/dl in males and ˃6mg/dl in females. Diagnosed patients of Chronic Gout qualifying the inclusion criteria were enrolled for clinical trial after obtaining their written consent and were randomly assigned into test and control groups. The basal clinical findings were compared with the findings observed at 7th, 14th day, 21th and 29th day. The lab investigations were done before and after the treatment. The findings were recorded on case record form. The basal clinical findings were compared with the findings. The difference if any observed was recorded in percentage and taken as the improvement caused by the respective treatment. Similarly, the basal findings of investigations were compared to the post treatment findings of the investigations and the improvement was recorded in case record form. All the observations in both groups were tabulated & statistical analysis was carried out with the help of biostatistician to known which drug is more effective clinically and in reducing the serum uric acid level. On the basis of history, clinical examination and investigations, the patients fulfilling the inclusion criteria were enrolled for the study after obtaining written voluntary consent. While those patients, who failed to fulfill the required inclusion criteria, were excluded from the study.

2.1. The selection of the subjects was made on the basis of following criteria:

a. Inclusion criteria 

1)  Irrespective of all genders.

2)  Patients between 18-65 years of age. 

3)  Patients Fulfilling the criteria of American College of Rheumatology (ACR) for diagnosing gouty arthritis including clinical features, laboratory and radiological finding, having serum uric acid level>7mg/dl in males and ˃6mg/dl in females. 

4)  Patients, who are ready to sign the informed consent, follow the protocol and willing to participate in clinical study voluntarily. 

b. Exclusion criteria 

1) Patients below 18 and above 65 years of age.

2) Pregnant and lactating mothers. 

3) Patients who fail to give consent. 

4) Patients of gout associated with any systemic disorder which interfere with patient study.

 5) Patients of gout associated with any severe arthritic condition such as rheumatoid arthritis, septic arthritis.

 6) Patients suffering from anemia and other blood dyscrasias like leukemia, haemophilia, etc 

7) Patients suffering from congenital gout.

 8) Any other disease other than Gout (Gouty arthritis).

Withdrawal Criteria: 

1) Failure to follow up (absence from the study for more than one month). 

2) Poor compliance to the protocol such as not using drug at regular basis.

 3) Any gross adverse effect. In case of possible minor adverse events such as burning, itching, swelling and redness in either group, the same was managed with appropriate drug.

2.2. Method of assessment of the disease

1. Subjective Parameters 

 Joint Pain 

Joint Swelling

Joint stiffness 

Restriction of Movements 

The data of subjective parameters was recorded on , 7th, 14th and 29th day of the study.

2. Objective parameters 

Serum uric acid level

CRP (quantitative) on day 0th and 29th

ESR

The objective parameters were assessed on 0th and 29th day of the study. 

2.3. Availability, dosage and mode of administration of test drug & control drug

Boozidaan (Pyrethrum indicum) The drug was purchased from the local Market, identified and authenticated from centre for Biodiversity &Taxonomy, Department of Botany, University Of Kashmir, No:F(Herbarium Specimen CBT/KU)21 and Voucher Specimen No. 4265-KASH Herbarium. Boozidaan (Pyrethrum indicum) was prepared by grinding and pulverizing the Crude drug at Zam Zam laboratory, Rangereth Srinagar. In the form of powder (safoof), the powder form of drug was packed in the form of 5 gm sachets. Each patients of test group was advised to take 5 gms of Boozidaan (Pyrethrum Indicum) powder with water once daily after breakfast for duration of 28 days. The control drug Febuxostat was purchased from local market under the trade name of Feboxa 80mg from RANBAXY. The tablets removed from the strips and then packed in sterile air tight packets for period of seven days in order to ensure blinding. Each patients of control group was advised to take a tablet of Febuxostat 80mg with water once daily after breakfast for period of 28 days.

Follow up

The clinical assessment of all groups was carried out after every 7th day. The findings were recorded on CRF (case report form). The basal clinical findings were compared with the findings observed at 7th, 14th day, 21th and 29th day. The lab investigations were done before and after the treatment. 

3. RESULTS AND OBSERVATIONS

The results of the study reveal that majority of the patients were between 40-60 years of age (53.34%), belonged to male gender (51.67%) and were muslim (100%). Majority of the patients were married (90%) belonging to middle class families (40%) having mixed dietary habits (100%) and maximum patients were from housewives group (45%) followed by businessmen (26.67%), government employees (16.67%), laborers (8%) and student (3.3%). Majority of patients in both the groups were having a balghami mizaj constituting about 60% in test group and 76.67% in control group.

3.1. Effect of drugs on subjective parameters 

Joint pain:

During the course of the study it was observed that joint pain was present in all the patient of Test group and Control group before treatment. After treatment joint pain was absent in 80.0% of the patients in test group and 36.67% patients in control group. The data showing the distribution of patients according to effect on severity of joint pain in the test group and control group reveals that there exists a high significant difference before and after the treatment among both test and control groups with a p-value (<0.0001*) which means that both Unani  and standard treatment is effective in resolving the severity of pain. To find out more effective drug between Test and control group, Chi Square test has been applied on the data for the difference of Test group and Control group it was found that χ2 = 11.589, df=1, P-value=<0.0001* indicating that improvement is highly significantly in test group compared to control group. (table1&2 and fig 1)


 

 

Table 1: Effect of test drug on joint pain

Distribution of patients as per severity of pain among test group as shown in Table 1

  Severity of pain

BT

AT

Total

No.

%age

No.

%age

No

%age

Absent

0.00

0.00

24.00

80.00

24.00

40.00

Mild

3.00

10.00

6.00

20.00

9.00

15.00

Moderate

26.00

86.67

0.00

0.00

26.00

43.33

Severe

1.00

3.33

0.00

0.00

1.00

1.67

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*

 

 

Table 2: Effect of control drug on joint pain

Distribution of patients as per severity  of  pain in control group as shown in Table 2

 Severity of pain

BT

AT

Total

No.

%age

No.

%age

No

%age

Absent

0.00

0.00

11.00

36.67

11.00

18.33

Mild

1.00

3.33

19.00

63.33

20.00

33.33

Moderate

28.00

93.33

0.00

0.00

28.00

46.67

Severe

1.00

3.33

0.00

0.00

1.00

1.67

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*

 

 

 image

Figure 1: Effect of test drug on joint pain

 


 

Joint swelling:

During the course of the study it was observed that joint swelling was present in all the patient of Test group and Control group before treatment. After treatment joint swelling was absent in all the patients in test group and 96.67% patients in control group. The data showing the distribution of patients according to effect on severity of joint swelling in the test group and control group reveals that there exists a high significant difference before and after the treatment among both test and control groups with a p-value (<0.0001*) which means that both unani and standard treatment is effective in resolving the severity of joint swelling. To find out more effective drug between Test and control group, Chi Square test has been applied on the data for the difference of Test group and Control group it was found that χ2 =1.017, Df=1, (Fisher’s Exact, P-value=1) 

 indicating that there is no significant difference in the efficacy of both drugs on joint swelling. Therefore, both the treatments are equally effective in resolving joint swelling. (table3&4 and fig 2)


 

 

Table 3:Effect of test drug on joint swelling

Showing  severity     of joint swelling before and after the treatment  in test group as shown in Table 3

 

BT

AT

Total

No.

%age

No.

%age

No

%age

No joint swelling

0.00

0.00

30.00

100.00

30.00

50.00

Palpable

5.00

16.67

0.00

0.00

5.00

8.33

Visible

23.00

76.67

0.00

0.00

23.00

38.33

Bulging beyond joint margins

2.00

6.67

0.00

0.00

2.00

3.33

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*

 

Table 4: Effect of control drug on joint swelling

Distribution of patients as per severity  of joint swelling before and after the treatment  in control group  as shown in Table 4

 

BT

AT

Total

No.

%age

No.

%age

No

%age

No joint swelling

0.00

0.00

29.00

96.67

29.00

48.33

Palpable

4.00

13.33

1.00

3.33

5.00

8.33

Visible

24.00

80.00

0.00

0.00

24.00

40.00

Bulging beyond joint margins

2.00

6.67

0.00

0.00

2.00

3.33

Total

30.00

100.00

30.00

100.00

60.00

100.00

 

image

Figure 2: Effect of test drug on joint swelling


 

Joint stiffness:

During the course of the study it was observed that joint stiffness was present in all the patient of Test group and Control group before treatment. After treatment joint stiffness was absent in 96.67% of the patients in test group and 86.67% patients in control group. The data showing the distribution of patients according to effect on severity of joint stiffness in the test group and control group reveals that there exists a high significant difference before and after the treatment among both test and control groups with a p-value (<0.0001*) which means that both unani and standard treatment is effective in resolving the severity of joint stiffness. To find out more effective drug between Test and control group, Chi Square test has been applied on the data for the difference of Test group and Control group it was found that χ2 = 1.964, Df=1, (Fisher’s Exact, P-value=0.353) indicating that there is no significant difference in the efficacy of   both drugs on joint stiffness. Therefore both the treatments are equally effective in resolving joint stiffness. However, almost 97% cases had no stiffness after the treatment in test group compared to 86.67% in control group. (Table 5&6 and fig.3)


 

 

Table 5: Effect of test drug on joint stiffness

Distribution of patients as per status of stiffness before and after the treatment in test group as shown in Table 5.

 Stiffness severity 

BT

AT

Total

No.

%age

No.

%age

No

%age

No stiffness

0.00

0.00

29.00

96.67

29.00

48.33

Sometimes for (5-10) mins

1.00

3.33

1.00

3.33

2.00

3.33

Daily for (10-30 mins)

10.00

33.33

0.00

0.00

10.00

16.67

Daily for (30-60 mins)

16.00

53.33

0.00

0.00

16.00

26.67

Daily for more than 1 hr

3.00

10.00

 0.00

0.00 

.00 

5.00 

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*

 

Table 6: Effect of control drug on joint stiffness

The distribution of patients as per status of stiffness before and after the treatment in control group as shown in Table 6.

 

BT

AT

Total

No.

%age

No.

%age

No

%age

No stiffness

0.00

0.00

26.00

86.67

26.00

43.33

Sometimes for (5-10) mins

1.00

3.33

4.00

13.33

5.00

8.33

Daily for (10-30 mins)

8.00

26.67

0.00

0.00

8.00

13.33

Daily for (30-60 mins)

21.00

70.00

0.00

0.00

21.00

35.00

Daily for more than 1 hr

0.00

0.00

 0.00

0.00 

0.00 

0.00 

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*

 

image

Figure 3: Effect of test drug on joint stiffness


 

Status of joint mobility:

During the course of the study it was observed that there was lack of Full Voluntary Movement in all the patient of Test group and Control group before treatment. After treatment Full Voluntary Movement was restored in 96.67% of the patients in test group and in all the patients in control group. The data showing the distribution of patients according to effect on status of joint mobility in the test group and control group reveals that there exists a high significant difference before and after the treatment among both  test  and control groups with a p-value (<0.0001*) which means that both   unani  and standard treatment is effective in restoring the joint mobility. To find out more effective drug between Test and control group, Chi Square test has been applied on the data for the difference of Test group and Control group it was found that χ2 = 1.017, Df=1, (Fisher’s Exact, P-value=1) indicating that there is no significant difference in the efficacy of  both drugs on restoring joint mobility. Therefore both the treatments are equally effective in improving the mobility of patients. (table 7&8 and fig.4)


 

 

Table 7: Effect of test drug on status of joint mobility

 Status of mobility before and after the treatment in test group as shown in Table 7

Mobility 

BT

AT

Total

No.

%age

No.

%age

No

%age

Full Voluntary Movement

0.00

0.00

29.00

96.67

29.00

48.33

Partial Voluntary Movement

3.00

10.00

1.00

3.33

4.00

6.67

Full movement if joint is moved by examiner

7.00

23.33

0.00

0.00

7.00

11.67

Partial movement if joint is moved by examiner

17.00

56.67

0.00

0.00

17.00

28.33

No movement at all

3.00

10.00

0.00

0.00

3.00

5.00

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*

 

Table 8: Effect of control drug on status of joint mobility

 Status of mobility before and after the treatment in control group  as shown in Table 8.

 Mobility

BT

AT

Total

No.

%age

No.

%age

No

%age

Full Voluntary Movement

0.00

0.00

30.00

100.00

30.00

50.00

Partial Voluntary Movement

1.00

3.33

0.00

0.00

1.00

1.67

Full movement if joint is moved by examiner

12.00

40.00

0.00

0.00

12.00

20.00

Partial movement if joint is moved by examiner

17.00

56.67

0.00

0.00

17.00

28.33

No movement at all

0.00

0.00

0.00

0.00

0.00

0.00

Total

30.00

100.00

30.00

100.00

60.00

100.00

P-value=<0.0001*