Ajphr 810041
Ajphr 810041
Ajphr 810041
www.ajphr.com
2020, Volume 8, Issue 1
ISSN: 2321–3647(online)
ABSTRACT
Cholecystitis is a medical condition where inflammation occurs in gallbladder. This condition
can be associated with or without the presence of gallstones. Bacterial infection accounts for
50% to 85% of the disease's onset. Since there is a close relationship between the biliary system
and the gut. In Unani system of medicine SBM and MDW, are compound formulation is
effective in the treatment of Amraz-e- Jigar and may be useful in the treatment of Warm-e-
Marara also. So the aim of this study is to evaluate the efficacy of Unani Formulation on
scientific parameters. This study was an open observational study, carried out on 40 patients. The
test drug was given in the form of decoction with 7 gm Majoon Dabeedulward with 50 ml
Sharbat Bazoori Motadil twice a day after meal for the period of 2 months. All the patients of
were assessed fortnightly on subjective parameters (0th, 15th, 30th 45th and 60th day) whereas
objective parameters were assessed before and after the treatment. The outcome of intervention
was analyzed using appropriate statistical methods. The subjective parameters of pain in
abdomen, nausea & vomiting, dyspepsia and loss of appetite were satisfactorily alleviated by the
test drugs and all the findings found in USG and CT scan were also seen to subside within the
protocol duration. The findings about the parameters suggest that the test drug was effective in
Warm-e-Marara and the cure was substantial. It reduced the subjective parameters as well as the
findings in USG and CT scan of the Warm-e-Marara patients.
Keywords: Acute Cholecystitis; Warm-e-Marara; Majoon Dabeedulward; Sharbat Bazoori
Motadil.
Please cite this article as: Alam MT et al., Clinical or Surgical Study of Warm-e-Mararah (Cholecystitis)
. American Journal of Pharmacy & Health Research 2020.
Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
INTRODUCTION
Cholecystitis is a medical condition where inflammation occurs in gallbladder.1 This condition
can be associated with or without the presence of gallstones.2 It is classified in to two types i.e.,
acute cholecystitis and chronic cholecystitis. 3 It is found both in men and women but may have a
propensity for certain populations.2
Acute cholecystitis is defined as inflammation of the gallbladder and is usually caused by
obstruction of the cystic duct,4 whereas Chronic cholecystitis is a prolonged, sub-acute condition
caused by the mechanical or functional dysfunction of the emptying of the gallbladder.3
Acute cholecystitis (AC) is one of the most common surgical diseases. Bacterial infection
accounts for 50% to 85% of the disease's onset. Since there is a close relationship between the
biliary system and the gut.5
Acute cholecystitis is most often caused by gall stones. Gall stones are one of the most common
disorders of the gastrointestinal tract, affecting about 10% of people in Western society and more
than 80% of people with gall stones are asymptomatic whereas acute cholecystitis develops in 1-
3% of patients with symptomatic gall stones.6
Acute calculous cholecystitis (ACC) is the most frequent complication of cholelithiasis and
represents one-third of all surgical emergency hospital admissions.7 According to WHO,
Gallstone disease is a major health problem in particularly, in developed world. It is also one of
the leading causes of digestion-related hospital admissions with high healthcare costs in these
countries.8
Helminthic infection (ascariasis) is a major cause of biliary disease in developing countries in
Asia, southern Africa, and Latin America. Obstruction of the cystic duct causes an inflammatory
process to start. This results in acute cholecystitis. If the inflammation persists it may cause
perforation or gangrene of the gall bladder.9 Over 90% of cases of acute cholecystitis result from
obstruction of the cystic duct by gall stones or by biliary sludge that has become impacted at the
neck of the gall bladder.10 Obstruction of the cystic duct causes the intraluminal pressure within
the gall bladder to increase and, together with cholesterol supersaturated bile, triggers an acute
inflammatory response. The trauma caused by the gall stones stimulates the synthesis of
prostaglandins I2 and E2, which mediate the inflammatory response. 11
Secondary bacterial infection with enteric organisms (most commonly Escherichia
coli, Klebsiella, and Streptococcus faecalis) occurs in about 20% of cases.12 biliary sludge is a
mixture of particulate matter and bile, and it may stimulate microlithiasis. If the sludge persists-
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for example, because the patient has already had several pregnancies or is receiving total
parenteral nutrition-gall stones can form.13 Acute cholecystitis (AC) is a life-threatening
emergency that commonly occurs as a complication of gallstones.14 Severe right upper quadrant
pain, abdominal guarding, fever, and a positive Murphy's sign with an elevated white blood cell
count are the classical clinical manifestations of AC.15
Although ultrasonography is typically the initial diagnostic examination in patients with
suspected AC, computed tomography and magnetic resonance imaging are commonly performed
to identify complications; cholecystography is recommended in patients with equivocal findings
on the other imaging modalities, as this technique has the highest diagnostic accuracy in the
diagnosis of AC. 16
Imaging studies are also helpful in the timely detection of complications associated with AC.
Although laparoscopic cholecystectomy is considered the gold-standard treatment for AC,17
percutaneous gallbladder drainage with or without cholecystectomy tube placement is a safe,
effective management technique for surgically high-risk patients with multiple medical
conditions.18
This treatment can be used as either a bridging therapy, with elective cholecystectomy performed
at a later time after improvement of the patient's condition, or as definitive treatment in
surgically unfit patients.19 Radiologists play a pivotal role in the initial diagnosis and
management of patients with AC.20 Cholescintigraphy is the most sensitive imaging modality for
cholecystitis.21 Complications of acute cholecystitis have a characteristic CT appearance and
include necrosis, perforation, abscess formation, intraluminal hemorrhage, and wall
emphysema.22 There is various allopathic medicines available for the management of
cholecystitis like ursodeoxycholic acids, NSAID, Opium derivatives etc., have various side
effects.23
Unani Scholars also described about Amraze Mararah, under the caption of Amraze Jigar, they
also mentioned that inflammation occurs in the Mararah is due to Ghaleez wa fasid ghiza,
ehtebas ghair tabayi. 24
Most of the Great Unani scholars like Hippocras, Galen, Zakaria Razi, Ali Ibn Abbas Majusi,
Ibn-e-Sina, Ismail Jurjani, Ibn-e-Hubal Baghdadi etc., are described about the pathophysiology
of this disease and also their treatment method by Mufarrad wa Murakkab Drugs like; Kasni,
Mako, Karafs, Tukhm Soya, Khare Khasak, Hajrul Yahud, Afsanteen, Duqu, Habbul Qilt, Sirka,
Arque Kasni, Arque Mako, Arque Ajwain, Majun Hajrul Yahood etc.25 Currently most of them
are scientifically proved for their lithotripsy, analgesic, hypolipidemic activities.26
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
So this study was conduct as a clinical trial using Unani formulation title as “Clinical or
Surgical Study of Warm-e- Marara (Cholecystitis)” on scientific parameters.
After obtaining ethical clearance from Institutional Ethical Committee, Deoband Unani Medical
College, Hospital & Research Centre, Deoband, as an open labeled interventional without
control pre and post analysis study, Sample size was 40 (both male & female) only
interventional group, Diagnosed case Warm-e-Marara and Patients who have agreed to sign the
informed consent form and follow up the protocol, Patients were kept under strict observation
and advised to come fortnightly in OPD for the assessment of study till the completion of study.
Sixty days study was divided into four visits of follow up, which were made at an interval of 15
days. At every visit, patients were asked about the progression or regression in their symptoms
and subjected to assess the clinical findings.
The study outcome measures of baseline are compared with each follow ups in terms of
subjective and objective parameters as per protocol. A total of 80 patients were screened, out of
which 40 cases fulfilling the inclusion criterion based on thorough history, clinical examinations.
Certain investigations were carried out with the aim to exclude the patients with pathological
conditions mentioned under exclusion criteria and to assess the efficacy of treatment group and
to establish the safety of the test drug.
Objective of The Study
To evaluate the efficacy of Unani formulation in Warm-e-Mararah (Cholecystitis) as
conservative treatment.
MATERIALS AND METHOD
The present clinical study entitled “Clinical or Surgical Study of Warm-e- Mararah
(Cholecystitis)” was conducted at OPDs of DUMC Hospital & Research Centre, Deoband (UP)
from June 2017 to September 2018. The study was executed after obtaining approval of the study
protocol from the Institutional Ethical Committee, Deoband Unani Medical College, Hospital &
Research Centre, Deoband. The study protocol comprises of following subheadings.
Criteria for selection of cases
Inclusion criteria:
Patients of age group between 30-55 years.
Patients of either sex.
Diagnosed case of cholecystitis
Radiological Evidence of Cholecystitis
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Patients who have agreed to sign the informed consent form and follow up the protocol.
Exclusion criteria:
Patients of age group between 30-55 years.
Patients below 30 years and above 55 years.
Uncontrolled Diabetes & Hypertension
Pregnant and lactating women.
Patient undergoing treatment for other serious illness.
Selection of subjects
After the screening, during the selection of the patients, complete history including general
physical and systemic examination was carried out and recorded on a prescribed case report form
which was designed according to the objectives of the study. A detailed history was recorded
regarding their chief complaints with duration, age, sex, religion, marital status, occupation,
address, socioeconomic status on the basis Kuppaswamy’s socioeconomic scale. Personal
history, treatment history, past history of any disease and family history were also recorded in a
predesigned proforma. After history taking, general physical examination was done with special
emphasis on height (in cm), weight (in kg), pulse rate/minute; blood pressure in mm of Hg, any
other positive finding during general physical examination was recorded in CRF. Likewise, a
careful systemic examination of cardiovascular system, respiratory system, renal system,
gastrointestinal system was also done to look for any findings of other serious illness. After that
detailed examination specific to the diabetes mellitus was carried out in all the patients.
Assessment of Temperament
Determination of temperament (Mizaj) was done on the based on Ajnas-e-Ashra (10 different
parameters) mentioned in Unani literature. These parameters have been shown in the table
attached with the case report form in annexure.
Informed consent
Patients coming under the inclusion criteria mentioned above were given the information sheet
having details regarding the nature of the study, the drug to be used, method of treatment etc and
explained verbally also about study. Patients were given enough time to go through the contents
of informed consent sheet. They were given the opportunity to ask any question and if they
agreed to participate in the study, they were asked to sign the informed consent form.
Investigations
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
Certain investigations were carried out with the aim to exclude the patients with pathological
conditions mentioned under exclusion criteria and to assess the efficacy of treatment group and
to establish the safety of the test drug.
Following investigations were done in each and every case before and after the treatment to
evaluate the efficacy of Unani formulation in warm-e-meda.
Total Bilirubin
SGOT
SGPT
Alkaline Phosphate
Blood Urea
Serum Creatinine
Endoscopy
Method of Collection of Data:
Clinical interview
Laboratory investigations.
Subjective parameters:
Pain in abdomen
Nausea & Vomiting
Dyspepsia
Loss of appetite
Objective parameters:
USG whole abdomen
CT whole abdomen
Study design:
The study was designed an open observational study.
Sample size:
The sample size was 40 diagnosed patients.
Allocation of subjects:
Forty research subjects were single arm as test group with sample size of 40.
Duration of protocol:
The treatment period was determined as 60 days.
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Descriptive and inferential statistical analysis has been carried out in the present study. Results
on continuous measurements are presented on Mean SD (Min-Max) and results on categorical
measurements are presented in Number (%). Significance is assessed at 5 % level of
significance. The following assumptions on data is made, Assumptions: 1. Dependent variables
should be normally distributed, 2. Samples drawn from the population should be random, Cases
of the samples should be independent
Student t test (two tailed, dependent) has been used to find the significance of study parameters
on continuous scale within each group. Chi-square/ Fisher Exact test has been used to find the
significance of study parameters on categorical scale between two or more groups, Non-
parametric setting for Qualitative data analysis. Fisher exact test used when cell samples are very
small.
Paired Proportion test has been used to find the significance of proportion in paired data. Smaller
percentage of Improvement becomes significant at lower tail compared to higher tail. Eg.
Improvement from 10% to 20% is difficult than the Improvement from 80% to 90%.
Significant figures
+ Suggestive significance (P value: 0.05<P<0.10)
* Moderately significant (P value: 0.01<P 0.05)
** Strongly significant (P value: P0.01)
Statistical software: The Statistical software namely SPSS 18.0, and R environment ver.3.2.2
were used for the analysis of the data and Microsoft word and Excel have been used to generate
graphs, tables etc.
RESULTS AND OBSERVATION
Study design: An observational clinical study
Table 1: Mizaj distribution of patients studied
Mizaj No. of patients %
Damvi 4 10.0
Safravi 28 70.0
Saudavi 8 20.0
Total 40 100.0
Table 2: Pain in Abdomen- An assessment at different time intervals of patients studied
Pain in Abdomen 0d 15 d 30 d 45 d 60 d % difference
0 0(0%) 1(2.5%) 5(12.5%) 10(25%) 21(52.5%) 52.5%
1 0(0%) 12(30%) 18(45%) 26(65%) 18(45%) 45.0%
2 12(30%) 18(45%) 16(40%) 4(10%) 1(2.5%) -27.5%
3 28(70%) 9(22.5%) 1(2.5%) 0(0%) 0(0%) -70.0%
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
Pain in Abdomen
70
0
60
1
50
Percentage 2
40 3
30
20
10
0
0d 15 d 30 d 45 d 60 d
Pain in Abdomen
Table 3: Nausea & Vomiting- An assessment at different time intervals of patients studied
Nausea & 0 d 15 d 30 d 45 d 60 d %
Vomiting difference
0 1(2.5%) 4(10%) 12(30%) 21(52.5%) 32(80%) 77.5%
1 3(7.5%) 18(45%) 23(57.5%) 18(45%) 8(20%) 12.5%
2 16(40%) 17(42.5%) 4(10%) 1(2.5%) 0(0%) -40.0%
3 20(50%) 1(2.5%) 1(2.5%) 0(0%) 0(0%) -50.0%
Total 40(100%) 40(100%) 40(100%) 40(100%) 40(100%) -
P<0.001**, 90% change, significant, paired proportion test
60 1
2
Percentage
50
3
40
30
20
10
0
0d 15 d 30 d 45 d 60 d
Pain in Abdomen
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
severe nausea & vomiting and only 1 patients had severe nausea & vomiting whereas nausea &
vomiting was reduced to moderate and mild in 17 and 18 patients, respectively and one patient
had no nausea & vomiting. The nausea & vomiting subsided continuously till sixty day of
treatment. On sixty day only one patient had severe nausea & vomiting and 32 patients had no
nausea & vomiting, 8 patients had mild nausea & vomiting. When the pre and post treatment
data was analyzed statistically using chi square test for proportions the nausea & vomiting
reduction was significant (p<0.001) in post treated group. (Table No. 3). The effect was due to
various drugs present in the Joshanda, Sharbat Bazoori Motadil and Majoon Dabeedulward.
SBM is established diuretic and the ingredients have documented anti-inflammatory activity.
25,26,27,28
Dyspepsia:
Dyspepsia associated with Warm-e-Mararah was found in all the 40 patients when enrolled in
the study.18 patients had severe dyspepsia and 19 had moderate dyspepsia. 15 day after the
administration of the test drugs it was found that there was 45% reduction in severe dyspepsia
and only 4 patients had severe dyspepsia whereas dyspepsia was reduced to moderate and mild
in 21 and 10 patients and five patient had no dyspepsia. The dyspepsia subsided continuously till
sixty day of treatment. On sixty day no patient had dyspepsia. When the pre and post treatment
data was analyzed statistically using chi square test for proportions the dyspepsia reduction was
significant (p<0.001) in post treated group. (Table No. 4). The effect was due to various drugs
present in the Joshanda, Sharbat Bazoori Motadil and Majoon Dabeedulward. SBM is
established diuretic and the ingredients have documented anti-inflammatory activity. 25,26,27,28
Loss of Appetite:
Loss of appetite associated with Warm-e-Mararah was found in all the 40 patients when enrolled
in the study.21 patients had severe loss of appetite and 19 had mild severe loss of appetite. 15
day after the administration of the test drugs it was found that there was 32% reduction in loss of
appetite and only 3 patients had severe loss of appetite whereas severe loss of appetite was
reduced to moderate and mild in 20 and 15 patients and one patient had no severe loss of
appetite. The severe loss of appetite subsided continuously till sixty day of treatment. On sixty
day no patient had severe loss of appetite and 26 patients had no complaint of loss of appetite, 13
patients had mild and one had moderate loss of appetite. When the pre and post treatment data
was analyzed statistically using chi square test for proportions the severe loss of appetite
reduction was significant (p<0.001) in post treated group. (Table No. 5). The effect was due to
various drugs present in the Joshanda, Sharbat Bazoori Motadil and Majoon Dabeedulward.
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
SBM is established diuretic and the ingredients have documented anti-inflammatory activity.
25,26,27,28
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
CONCLUSION
The findings about the parameters suggest that the test drug was effective in Warm-e-Mararah
and the cure was substantial. The effect was due to various drugs present in the Joshanda,
Sharbat Bazoori Motadil and Majoon Dabeedulward. SBM is established diuretic and the
ingredients have documented anti-inflammatory activity. Moreover, MDW has been documented
as liver tonic, anti-oxidant, and anti-cancer drug. Since Gall bladder is considered as part of liver
in Unani and presently it has the function of concentrating bile salts, the above drugs may have
acted upon the inflammation in the similar way as in Hepatitis.
The subjective parameters of pain in abdomen, nausea & vomiting, dyspepsia and loss of
appetite, were satisfactorily alleviated by the test drugs and all the findings found in USG and
CT scan were also seen to subside with in the protocol duration.
The findings about the parameters suggest that the test drug was effective in Warm-e-Mararah
and the cure was substantial. It reduced the subjective parameters as well as the findings in USG
and CT scan of the Warm-e-Merarah patients.
The study is observational one with 40 patients. It had inherent limitation of confounding.
Further research is needed in large number of patients with suitable control group to fine tune the
results obtained from present study.
SUMMARY
The present clinical study entitled “Clinical or Surgical Study of Warm-e-Marara
(Cholecystitis)” was conducted at OPDs of DUMC Hospital & Research Centre, Deoband (UP)
from June 2017 to September 2018. The study was executed after obtaining approval of the study
protocol from the Institutional Ethical Committee, Deoband Unani Medical College, Hospital &
Research Centre, Deoband. The study protocol comprises of following subheadings.
Mizaj distribution of patients studied:
28(70%) patients of cholecystitis were Safravi Mizaj and 8(20%) were Saudavi Mizaj and
3(7.5%) in Damvi Mizaj.
Effect of Research Drug on Subjective parameters:
Pain in Abdomen:
Pain associated with Warm-e-Mararah was found in all the 40 patients when enrolled in the
study, 12 patients had severe pain and 12 had mild pain. After the administration of the test drugs
it was found that there was 70% reduction in severe pain.
Nausea & Vomiting:
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Alam et al., Am. J. Pharm Health Res 2020;8(1) ISSN: 2321-3647
Nausea & vomiting associated with Warm-e-Mararah was found in all the 39 patients when
enrolled in the study.20 patients had severe nausea & vomiting and 16 had mild nausea &
vomiting. After the administration of the test drugs it was found that there was 50% reduction in
severe nausea & vomiting.
Dyspepsia:
Dyspepsia associated with Warm-e-Mararah was found in all the 40 patients when enrolled in
the study.18 patients had severe dyspepsia and 19 had moderate dyspepsia. 15 day after the
administration of the test drugs it was found that there was 45% reduction in severe dyspepsia.
Loss of Appetite:
Loss of appetite associated with Warm-e-Mararah was found in all the 40 patients when enrolled
in the study. 21 patients had severe loss of appetite and 19 had mild severe loss of appetite. 15
day after the administration of the test drugs it was found that there was 32% reduction in loss of
appetite.
Effect of Research Drug on Objective parameters:
USG Whole Abdomen:
USG finding before treatment showed gall bladder enlargement in – patients and normal findings
in – patients before administration of the test drugs. After the administration of the test drugs 31
patients had normal gall bladder whereas 9 patient had persisted with the enlargement of gall
bladder. When the pre and post treatment patients USG findings was analyzed statistically using
chi square test for proportions the inflammation reduction was significant (p<0.001) in post
treated group.
CT-Scan:
CT scan finding before treatment showed gall bladder enlargement in 40 patients and normal
findings in none patients before administration of the test drugs. After the administration of the
test drugs 32 patients had normal gall bladder whereas 8 patient had persisted with the
enlargement of gall bladder. When the pre and post treatment patients CT findings was analyzed
statistically using chi square test for proportions the inflammation reduction was significant
(p<0.001) in post treated group.
Effect of Research Drug on Safety parameters
All the hematological parameters of Hb%, TLC and DLC, Liver function parameters of SGOT
and SGPT, and kidney function parameters of blood Urea and serum creatinine as seen from the
result data were found within normal range before and after the drug administration.
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