Wudpecker Journal of Pharmacy and Pharmocology Vol. 1(1), pp. 005 - 009, November 2012 Available online at http://www.wudpeckerresearchjournals.

org 2012 Wudpecker Research Journals

Full Length Research Paper

Clinical evaluation of herbal coded formulation urolith for treatment of urolithisis

Qalb E Saleem, Abdul Hannan, Khan Usmanghani, Halima Nazar, E. Mohiuddin, M. Akram
Faculty of Eastern Medicine, Hamdard University Karachi, Pakistan. Accepted 15 October 2012 A study was conducted to investigate the efficacy of herbal coded formulation Urolith in comparison to another herbal medicine Dawa e Pathri for treatment of urolithliasis. One hundred patients with urolithiasis were randomly assigned into test and control with 50 in each group. The test group was treated with Urolith and control group was treated with Dawa e Pathri. Comparison of data recorded by physician relating to variables showed significant difference between test and control drug (p<0.05). The efficacy of Urolith was superior as p=0.03. Urolith is more effective than Dawa e Pthri in the treatment of Urolithiasis. Key words: Urolith, Dawa e Pathri, urolithiasis, efficacy. INTRODUCTION Urolithiasis is a major public health problem with serious complications. Urolithiasis has become a global problem in spite of advances in modern science. Patients with urolithiasis constitute an important part of everyday urological practice. The optical management of this disease requires knowledge of diagnostic procedures and treatment (Tiselius, 2001; Smith and Rosenfield, 1995; Kobayashi, 2003; Sudah, 2002). It leads to various complications like kidney failure etc. Owing to these complications, the researchers of different system of medicine are concentrating themselves for the development of the new urolithotriptic drugs. Different anti-urolithiasis drugs of main stream medicine have potent and effective action, but the long term use of these drugs results in development of various side effects. Therefore, there is a need to develop safe and effective drug for the management of urolithiasis. Thus, this study was planned to evaluate the efficacy of herbal coded formulation in the management of urolithiasis on scientific parameters. Herbal treatment could be an alternate and complimentary therapy that requires evidence based approach to eliminate urinary stones. Unani medicines are in common use by the most of the population of Pakistan and India. Accurate knowledge of the plants and their medicinal activities are held by only a few people. Unfortunately these invaluable knowledge and art of healing that have been religiously preserved for generations are not being passed on to the younger generation of today. Much of this traditional knowledge on medicinal plants will likely be lost with the current elderly generation of healers. Documentation and clinical trial study of this indigenous knowledge must therefore be accorded high priority if the future generation intends to benefit from it in overcoming some of the new emerging problems in health, agriculture and pharmaceutical industry. It is the aim of present investigation that herbal medicine be evaluated in randomized clinical trials for its efficacy for the treatment of urolithiasis. Study design The study was carried out from June 2007 to June 2009. The patients included in the trial were those reporting to the Outpatient Department. They were thoroughly examined for clinical signs and symptoms. Their lab reports were recorded. Patients with all types of urolithiasis, that was either newly detected or having previous history was informed about the trial and were enrolled after signing consent form. Urine analysis, x-ray and ultrasonography were performed. Patients with satisfactory results for these studies were considered for drug therapy. Patients with recent history of urinary tract infection, diabetes mellitus, kidney failure, renal failure or cerebrovascular accidents were excluded from the study.

*Corresponding author E-mail: makram_0451@hotmail.com.

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50 patients (aged 20 TO 60 years) were randomized to receive Urolith (Dorema ammoniacum = 3gm, Nepeta Hindostana=3gm, Rauwolfia serpentine=2gm, Valeriana officinalis=3gm and Bombax mori=5gm) in the doubleblind, parallel group trial. Then the patients received either 500mg tablet, two tablets thrice a day TID equally divided doses for three to four weeks. Selection of doses was on the basis of our clinical practice and doses were adjusted whenever necessary. At the end of 4 weeks of drug therapy Urine D/R, KUB X-ray or ultra-sound were repeated, drug therapy was tapered off and patients numbers were decoded. Results are expressed as mean SEM. A patient was categorized as a responder if his or her stone size at the end of the study period has become less or removed as compared to the initial stage. SETTING This case controlled examination based study was conducted at Naveed-e-Sehat Dawakhana, Near Jubli Cinema, Karachi and Shifa ul Mulk Memorial Hospital for Eastern Medicine Hamdard University on the patient living in the rural areas of 27 to 70 villages surrounding Madinat-ul-Hikamah Hamdard University, Karachi. Hamdard, Karachi. Sample selection The sample was selected from the outpatients enrolled in Shifa-ul-Mulk Memorial Hospital for Eastern Medicine and on the basis of preliminary clinical examination of the patients who were suffering from urolithiasis, were referred to the project officer and upon the basis of inclusion and exclusion criteria the patient mashed as candidate were selected. The study period include 2 years time from 2007 to 2009. Among this population all the patient suffering from were interviewed immediately and upon their consent to participate they were grouped as case and control group. Data collection Data collected for this study included filling questionnaire through personal interview, personal observation, use of case record, file and documents. The clinical trial proforma attached here which clearly specifies the clinical feature and information. Statistical analysis For comparison of the lithotriptic activity of these 2 agents, reduction in size of the stone or removal of stone from 0 to 4 weeks was calculated as the area under the

curve (AUC) using the trapezoidal rule. Statistical analysis were performed using SPSS in cooperation with Mr. Syed Tashfeen Akhter, Assistant Manager, Takaful Pakistan Limited, using excel and access database software, the Chi Square are used for paired data. All differences were considered statistically significant by generating a p-value from Chi square test statistics. Study limitations The data was adjusted based on the number of cases in the light of demographic factor using statistical methods like multinomial logistic regression. The data were composed in separate group. The groups were compared after random selection of subject in equal proportion using SPSS software. The subject were divided into two groups the case and the control groups. Finally, the case and control groups were compared separately. Ethical issues Ethical committee clearance and permission obtained whenever necessary considering: was

a) Informing each participant of the study and interviewing and examining the patient who consented to participate in the study. b) Identity will not be revealed and the data would be kept strictly confidential. c) Copy of the entire data will be made available to the Shifa ul Mulk Memorial Hospital. Inclusion criteria The criteria for inclusion are: Patients between age group of 20 to 60 years. Both genders are eligible for study. Evidence of urolithiasis Patients living in Karachi, Pakistan. All socio-economical classes including lower, middle and upper. Acceptable for outpatient stone management Exclusion criteria The criteria for exclusion are: Urinary tract infection Known anatomical genitourinary abnormalities, or prior GU surgeries Diabetes Ulcer disease

(GU)

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Table 1. Mean age of patients

CONTROL PATHRI)

DRUG

(DAWA-A-

TEST DRUG (UROLITH)

Total

Treatment Group Male Female Total Male Female Total Male Female Total

Mean age 33.95 36.46 35.36 37.48 37.80 37.64 35.83 37.09 36.50

Std. Deviation 10.594 10.651 10.592 11.439 8.190 9.847 11.075 9.504 10.239

Number (n) 22 28 50 25 25 50 47 53 100

Table 2. Distribution of age group in total patients. Age Group 20 25 Years 25 30 Years 30 35 Years 35 40 Years 40 45 Years 45 50 Years 50 55 Years 55 60 Years Total Treatment Group Test (n) Control (n) 6 8 4 7 4 8 15 12 9 6 6 3 2 1 4 5 50 50 Total (n) 14 11 12 27 15 9 3 9 100

Table 3. Urolithisis sign and symtoms.

Burning Micturation: Dysurea Haematurea Oligourea Right renal colic Left renal colic

At base line After treatment At base line After treatment At base line After treatment At base line After treatment At base line After treatment At base line After treatment

No significane difference between test and control group No significant difference between test and control group No significane difference between test and control group Significant difference between test and control group No significane difference between test and control group No Significant difference between test and control group No significane difference between test and control group No Significant difference between test and control group No significane difference between test and control group No Significant difference between test and control group No significane difference between test and control group No Significant difference between test and control group

P value=1 P value:1 P value=1 P value:0.03 P value=.537 P value:1 P value=.399 P value:1 P value=.79 P value:1 P value=.177 P value:1

Table 4. Ultrasound KUB in total patients at baseline.

Complaint at Baseline Calcium Oxalate Calcium Phosphate Uric Acid Total

Ultrasound KUB

Treatment Group Control Test (Urolith) (Dawa-a-Pathri) 35 34 8 10 7 6 50 50

Total (n) 69 18 13 50

p value

0.85

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Table 5. Ultrasound KUB in total patients at after treatment. Treatment group Control Test (Urolith) (Dawa-a-Pathri) 04 11 46 39 50 50 Total (n) 15 85 50

Complaint at after treatment Calcium Oxalate Complete Improvement Total

p value

Ultrasound KUB

0.04

Osteoporosis Pregnancy Psychiatric disorder History of hypersensitivity to tamsulosin or corticosteroids Spontaneous stone expulsion in the ED Largest stone dimension .9mm Concurrent use of vardenafil (Levitra) Solitary kidney Transplanted kidney Renal insufficiency Fever Prisoners or wards of state RESULTS AND DISCUSSION This study was under taken as an observational paradigm in which an attempt was made to explore the urolithiasis patients taking herbal medicines so as to assess their efficacy. The collected data of 100 patients, 47 were males while 53 were female patients The patients gender, age, and baseline clinical features at the time of enrolment were recorded in both treatment arms. The age distribution of over all patients, for Urolith and Dawa-a-Pathri are shown in Table 1. All the patients were clearly categorized as having Urolithiasis. The demographic and baseline characteristics of the patients included in the groups evaluable for efficacy were found to be similar for the two treatment groups and were comparable to those of the intent-to-treat population as p>0.05. All of the patients recruited in this study were categorized in different class interval ranging from 20 years of age to 60 years of age as shown in table 2. All patients had one or more pretreatment symptoms of Urolithiasis, which were almost same in both treatment groups as p >0.05 in table 3 as mentioned below. Lab investigation response Abdominal ultrasonography Clinically relevant ultrasound KUB at base line with Urolith and Dawa-a-Pathri were found to be similar in

both groups all patients enrolled with Urolithiasis having different type of stones i.e. calcium oxalate, calcium phosphate and uric acid. In test groups out of 50 patients, calcium oxalate were found in 35 cases, calcium phosphate were found in 08 cases and uric acid were found in 07 cases. Whereas, in control group calcium oxalate was found in 34 cases, calcium phosphate was found in 10 cases and uric acid were found in 06 cases. After applying Chi-square and Fishers Exact Test p value was calculated 0.85, which is greater than 0.05 as shown in table 4. After treatment p value was 0.04 as shown in table 5 that indicates the efficacy of both medicine. DISCUSSION Herbal coded formulation contains medicinal plants that are commonly prescribed to treat kidney stones. Medicinal plants used in this formulation are ethnomedicinally paramount in Unani System of Medicine to treat various diseases of urinary tract. These medicinal plants hold rich source of secondary metabolites. In this study, an attempt has been made to investigate efficacy of this formulation to treat kidney stones. Mi et al. (2012) has reported the antiurolithic effect and the possible mechanisms of Desmodium styracifolium and Pyrrosiae petiolosa in rats. Prasad et al. (1993) has reported the antilithiatic activity of Musa (Paradisiaca Linn. cultivar)--"Puttubale" stem juice in albino rats. Khan et al. (2011) has reported the antiurolithic activity of Origanum vulgare through multiple pathways. Harsoliya et al. (2011) has reported the efficacy of ethanolic extracts of Bergenia ligulata, Nigella sativa and combination on calcium oxalate urolithiasis in rats. Garimella et al. (2001) has reported the in vitro antilithiatic activity of seeds of Dolichos biflorus and rhizome of Begenia ligulata wall. Basir et al. (2009) has reported the antiurolithic effect of Bergenia ligulata rhizome. Mekap et al. (2011) has reported the antiurolithiatic activity of Crataeva magna Lour. Bark. Malini et al. (2000) has reported the protective effect of triterpenes on calcium oxalate crystals-induced peroxidative changes in experimental urolithiasis. Varatharajan et al. (2008) has reported the antiurolithic effect of lupeol and lupeol linolate in experimental hyperoxaluria. Shelkea et al. (2011) has reported the nephroprotective activity of ethanolic extract of stem

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barks of Crataeva nurvala Buch Ham. Aslam et al. (2011) has reported the antiurolithic activity of Origanum vulgare. Sridhar et al. (2011) has reported the antinephrolithiatic effect of Crataeva magna lour. Dc. root on ethylene glycol induced lithiasis. Conclusion Urolith is more effective than the Dawa e Pathri in the treatment of urolithiais as determined by p value <0.03. Therefore control drug showed lesser efficacy than the test drug in its compliance to treat urolithiasis. The control drug exhibited side effect like nausea and vomiting, where the test drug did not display or show any untowards manifestation associated with the use of this medication and found acceptability by all treated patients. REFERENCES Aslam K, Samra B, Saeed R, Anwar H (2011). Antiurolithic activity of Origanum vulgare is mediated through multiple pathways, BMC Complement Altern Med., 11: 96-100. Basir S, Gilani AH (2009). Antiurolithic effect of Bergenia ligulata rhizome, an explanation of underlying mechanisms. J. Ethnopharmacol., 122(1): 106-116. Garimella TS, Jolly CI, Narayanan S (2001). In vitro study on antilithiatic activity of seeds of Dolichos biflorus and rhizome of Begenia ligulata wall. Phytother. Res., 15(4): 351-356. Harsoliya MS, Pathan JK, Khan N, Bhatt D, Patel UM (2011). Effect of ethanolic extracts of Bergenia ligulata, Nigella sativa and combination on calcium oxalate urolithiasis in rats. Int Drug Formulation Res., 2(2): 268280. Khan A, Bashir S, Khan SR, Gilani AH (2011). External use is beneficial in arthritis, Antiurolithic activity of Origanum vulgare is mediated through multiple pathways, BMC Complement Altern. Med., 17(11): 9699.

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