Indrani K Thesis
Indrani K Thesis
Indrani K Thesis
nj N
nj
xij
j x.
K N
j x x
S
n
i
1
1
2
2
1
) . 1 (
1
) .. . (
1
1
2
2
2
K
x j x nj
S
n
i
F=S
2
2
/S
1
2
Which follows F distribution (K-1, N-K)
2.Tukey test
D=Q
J N
MSE
/
, N is the total number of subjects and MSE is the mean square error in
ANOVA, J is the number of groups to be compared
EXPERIMENTAL STUDY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 137
3. Student t test (Two tailed, independent)
) 2 / 1 1 / 1 (
) ( ) (
2
2 1
2 1
n n s
x x
t
Where
2 2 1
) 2 2 ( ) 1 2 ( ) 1 1 ( ) 1 1 (
2
1
2 2
1
1 2
n n
x x n x x n
s
n
i
n
i
4. Student t-test for paired comparisons
Objective: To investigate the significance of the difference between single population
means. No assumption is made about the population variances
n s
x x
t
/
) 2 1 (
where
1 / ) (
2
n d di s
and di is the difference formed for each pair of observations
5.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 SAS 9.2, SPSS 15.0, Stata 10.1,
MedCalc 9.0.1 ,Systat 12.0 and R environment ver.2.11.1 were used for the analysis of
the data and Microsoft word and Excel have been used to generate graphs, tables etc.
Acknowledgement:
Dr.K.P.Suresh, Scientist (Biostatistics), National Institute of Animal Nutrition &
Physiology, Bangalore-560030
Study design: A Comparative Evaluation study
EXPERIMENTAL STUDY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 138
Table 55: Comparative Evaluation of Interventional treatment on Temperature
Group Baseline Treatment period Difference
at 4
th
hour
P value
Initial Ind. Of
Pyrexia
1 hour 2 hour 3 hour 4 hour
Group
I(Control)
34.000.45 34.920.58 35.470.64 35.750.61 35.980.66 36.420.49 2.42 <0.001**
Group II
(Standard)
33.870.45 34.550.12 34.460.35 34.030.26 33.850.31 33.680.38 0.18 0.058+
Group A1 33.781.23 34.601.36 34.531.03 33.761.19 33.631.17 33.501.18 0.28 0.016*
Group A2 32.900.86 34.250.8 33.881.35 33.181.29 32.880.87 32.400.55 0.38 0.191
Group C1 34.470.61 35.470.55 35.120.56 34.70.64 34.530.45 34.350.52 0.12 0.220
Group C2 34.470.41 36.50.45 35.400.3 35.030.33 34.530.37 34.450.38 0.017 0.611
Group C3 34.130.29 35.080.58 34.670.4 34.280.25 34.130.29 33.850.31 0.28 0.023*
P value 0.006** <0.001** 0.011** <0.001** <0.001** <0.001** - -
Table 56: pair wise comparison of Temperature (difference)
Group
Baseline Treatment period
Initial
Ind. Of
Pyrexia
1 hour 2 hour 3 hour 4 hour
Group I-II 0.13 0.37 1.01 1.72 2.13 2.73
Group I-A1 0.22 0.32 0.93 1.99 2.35 2.92
Group I-A2 1.10 0.67 1.58 2.57 3.10 4.02
Group I-C1 -0.47 -0.55 0.35 1.05 1.45 2.07
Group I-C2 -0.47 -1.58 0.07 0.72 1.45 1.97
Group I-C3 -0.13 -0.17 0.80 1.47 1.85 2.57
Group II-A1 0.08 -0.05 -0.07 0.27 0.22 0.18
Group II-A2 0.97 0.30 0.58 0.85 0.97 1.28
Group II-C1 -0.60 -0.92 -0.66 -0.67 -0.68 -0.67
Group II-C2 -0.60 -1.95 -0.94 -1.00 -0.68 -0.77
Group II-C3 -0.27 -0.53 -0.21 -0.25 -0.28 -0.17
EXPERIMENTAL STUDY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 139
Table 57: pair wise comparison of Temperature (p value)
Group
Baseline Treatment period
Initial
Ind. Of
Pyrexia
1 hour 2 hour 3 hour 4 hour
Group I-II 1.000 0.974 0.331 0.006** <0.001** <0.001**
Group I-A1 0.998 0.988 0.363 0.002** <0.001** <0.001**
Group I-A2 0.108 0.691 0.016* <0.001** <0.001** <0.001**
Group I-C1 0.897 0.843 0.984 0.219 0.009** <0.001**
Group I-C2 0.897 0.010* 1.000 0.649 0.009** <0.001**
Group I-C3 1.000 1.000 0.545 0.027* <0.001** <0.001**
Group II-A1 1.000 1.000 1.000 0.996 0.997 0.998
Group II-A2 0.211 0.991 0.869 0.455 0.216 0.022*
Group II-C1 0.732 0.330 0.785 0.719 0.558 0.503
Group II-C2 0.732 0.001** 0.411 0.269 0.558 0.338
Group II-C3 0.993 0.861 0.999 0.997 0.988 0.999
Table 58: Comparative Evaluation of Interventional treatment on Temperature
Group
Baseline Treatment period
Initial
Ind. Of
Pyrexia
1 hour 2 hour 3 hour 4 hour
Group A1 33.781.23 34.601.36 34.531.03 33.761.19 33.631.17 33.501.18
Group A2 32.900.86 34.250.8 33.881.35 33.181.29 32.880.87 32.400.55
Difference (A1-A2) 0.88 0.35 0.65 0.58 0.75 1.10
P value (A1-A2) 0.304 0.980 0.755 0.860 0.500 0.073+
EXPERIMENTAL STUDY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 140
Table 59: Comparative Evaluation of Interventional treatment on Temperature
Group
Baseline Treatment period
Initial
Ind. Of
Pyrexia
1 hour 2 hour 3 hour 4 hour
Group C1 34.470.61 35.470.55 35.120.56 34.70.64 34.530.45 34.350.52
Group C2 34.470.41 36.50.45 35.400.3 35.030.33 34.530.37 34.450.38
Group C3 34.130.29 35.080.58 34.670.4 34.280.25 34.130.29 33.850.31
Difference
Group C1-C2 0.00 1.03 0.28 0.33 0.00 0.10
Group C1-C3 0.33 0.38 0.45 0.42 0.40 0.50
Group C2-C3 0.33 1.42 0.73 0.75 0.40 0.60
P value
Group C1-C2 1.000 0.205 0.995 0.986 1.000 1.000
Group C1-C3 0.978 0.968 0.945 0.959 0.937 0.790
Group C2-C3 0.978 0.027* 0.641 0.600 0.937 0.622
EXPERIMENTAL STUDY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 141
Table 60: Comparative Evaluation of Interventional treatment on Temperature (A
Comparison between group A and group C)
Grou
p
Baseline Treatment period
Differen
ce at 4
th
hour
P
value Initial
Ind.
Of
Pyrexi
a
1 hour 2 hour 3 hour 4 hour
Grou
p A
33.34
1.11
34.43
1.08
34.211.
19
33.44
1.22
33.29
1.07
33.00
1.07
0.327 0.015*
Grou
p C
34.350.
46
35.68
0.79
35.06
0.51
34.67
0.52
34.40
0.41
34.22
0.48
0.14
0.009*
*
P
value
0.010*
0.001*
*
0.035*
0.008*
*
0.006*
*
0.004*
*
- -
.
Discussion
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 142
DISCUSSION
This study entitled with Comparative evaluation of antipyretic activity of two
preparations of Mrithyunjaya rasa (Bhaishajya Ratnavali) in experimentally
induced pyrexia in albino rats is discussed under following headings :-
1. Review of literature
2. Pharmaceutical study
3. Analytical results
4. experimental results
1.Review of literature:-
There are Twenty two Preparations available under name of Mrithyunjaya rasa out
of which Ten are in Jwara adhikara, One each in Prameha adhikara, Athisara Adhikara,
Panduroga adhikara, Udararoga adhikara, Kshayaroga adhikara, Sarvaroga adhikara,
Aristanasha adhikara, Two each in Sannipatharoga adhikara, , Rasayana adhikara.
Many formulations under the name of Mrithyunjaya rasa may be due to their common
properties i.e., quicker action, high potency, ability of curing the diseases without failure.
Among these Mrithyunjaya rasa of Jwaradhikara can be Categorized as -
Kajjali yogas-8
Hingula yogas-2
Haratala having kajjali\hingula yogas-2
Vathsanabha rahitha kajjali\hingula yogas-3
Yogas nothaving kajjali\hingula-1
Almost all are Kharaliya Yogas with showing range of dosage from one Gunja to one
Masha.
Two of the them are explained in Bhishajya rathnavali which has very few ingredients,
easily available in the market and economical in cost. Most of the ingredients are known
to be having antipyretic action
Mrithyunjaya rasa(1) contains 1 part of gomutra shodhita vatsanaba(Aconitum
ferox), shudda gandaka(Sulphur), maricha(Piper longum), shudda tankana(Borax), and
kana(Piper nigrum), 2 part of jambeera rasena shodita hingula(Cinnabar).These drugs
founded into powder in khalva yantra and mudga pramana vati is prepared.It is useful for
all kind of jwara taken along with hoeny.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 143
Mrithyunjaya rasa(2) contains 1 part of shudda parada(Mercury), 2 part of shudda
gandaka(Sulphur), 4 parts of shudda tankana(Borax), 8 parts of shudda
vatsanaba(Aconitum ferox), 16 parts of shudda dhatturabeeja(dattura stramonium) 32
parts of trikatu[maricha(Piper longum), adraka(Zingiber offcinale) and kana(Piper
nigrum)].Kajjali is prepared , then powder of these drugs given bhavana with dhattura
moola(dattura stramonium)swarasa and masha pramana vati is prepared It is useful for
all kind of Jvara.
Among these two preparations common ingredients are Gandhaka, Vathsanabha,
Tankana, Maricha, Pippali.
2.Pharmaceutical study:-
Gandhaka Shodhana:
In present study , Gandhaka Shodhana was done by Swedana & Dalana methods, using
milk & Grutha respectively as a Medias for Shodhana. Different Medias have been
mentioned for Gandhaka Shodhana but milk is considered to be best among those
because it helps in minimizing the unwanted teekshna guna of Gandhaka without
destroying its medicinal property by its properties like Madura vipaka, sheetha veerya,
and snigdha guna.
During Swedana, the powdered Sulfur on boiling in milk, it may get purified by removal
of fat-soluble impurities from it. The organic sulphur present in the protein of milk might
have a role in increasing bioavailability of inorganic sulphur. Due to which Gandhaka
will be bio-compatible and nontoxic.
The change in colour of milk from white to yellowish cream and sulphur smell may
indicate the dissolution of fat soluble sulphur content in the milk.
Sulphur can melt at two different temperatures
1. If heated rapidly, it melts at 112.8
0
C
2. But if heated slowly it will melt only at 118.6
0
C
In this case sulfur is melted by steady rise of temperature and crystallizes. Here the
second way of melting takes place.
During Dalana procedure, steady rise in temperature causes Gandhaka to melt and dribble
down through cloth in to vessel, leaving behind physical impurities like mud, stone etc.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 144
Due to reaction with air, Liquefied Sulfur will crystallize. The Grutha contains large
amount of fatty acids which is proved to be anti-toxic & this might have helped to
reduce the harmful effect of Gandhaka during the process of melting.
Total amount of loss was 15gms. This is due to elimination of unwanted substances,
dissolution of powdered Gandhaka in milk during Swedana and adherence of Gandhaka
to the cloth during Dalana.
Hingula Shodhana:-
At present study Hingula Shodhana was done by Bhavana method.
By Bhavana as Shodhana procedure along with the elimination of the blemishes present
in the drug, it is possible to reduce particle size of the drug which will help for the quick
absorption. Due to the action of Nimbuka rasa, mild acid soluble impurities may be
removed and increase in the bioavailability of the drug.
There was increase of 20gms after Shodhana may be due to presence of cellulose, sugar,
potassium citrate etc in Nimbuka Swarasa.
Hingulotta Parada:-
At present study Hingulotta Parada was done by Urdvapatana method
An addition of nimbu rasa during Hingula Shodhana, it is observed that there may be
reaction taking place between Mercury sulphide and Citric acid which might have helped
in extraction of chemically detoxifiable impurities from Hingula. In classics it was told
that Mardana of Hingula with Nimbuka Swarasa for Paradavisleshartham.
During the process , advantage of using Hingula power was observed which may be due
to better agnipaka , more availability of surface area and hence maximum amount of
disassociation of mercurial molecules from the processed Hingula.
During the Urdvapatana process , sulphur smell was appreciated due to the release of
SO
2
through micro pores of earthen pot.
For the Urdvapatana procedure, heat was given was750
0
c because,Cinnabar
disassociates at 620
0
c in this process , it needs more than 700
0
cto get the extraction of
mercury accomplished. In this process mercury releases first at 357.5
0
cof heat and get
vaporized which by nature goes upwards and due to lower temperature there, gets its
natural form of small globules or powder and get stuck to the inner portion of the upper
pot. The presence of water on the back of the upper pot brings down the heat and helps in
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 145
avoiding escaping of mercury and quicker condensation. The water may have to be
changed whenever it gets heated up in order to get faster condensation of mercury.
The colour of Sulphur changes as per the variation of temperature subjected to it.
At 350
0
c it turns black. So the blackish suit which was observed is burnt sulphur.
Total gain of Parada was 74gms. Since it was enough for further study repetition of
procedure to obtain the Parada completely from Hingula was not done.
Vathsanabha Shodhana:-
In present study Vathsanabha Shodhana was done by keeping it in Gomutra in atapa for
3days.
By this method, the impurities dissolved in alkalis can be separated . The ugrata of
vishatava of Vathsanabha may be reduced. It might help in minimizing the unwanted
teekshna guna of Vathsanabha without destroying its medicinal property.
The outer covering of Vathsanabha was easily peeled off and made into small pieces.
Due to influence of Gomutra, the shelf life of Vathsanabha found to be increased.
Dattura Shodhana:-
In present study Dattura Shodhana was done by adopting Swedana in Godugdha.
In milk it may get purified by removal of fat-soluble impurities from it.
It might help in minimizing the unwanted teekshna guna of Dattura without destroying its
medicinal property.
Tankana Shodhana:-
In present study Tankana Shodhana was done by Nirjalikarana procedure.
There was huge loss of weight because of evaporation of water.
3.Analytical study
The Physico-chemical tests like Ash value, Acid insoluble ash and loss on drying will
help to understand characteristic properties of a drug
Atomic absorption spectroscopy, to estimate quantitative and XRD test to know the
complete picture of the compound and element.
Ash value:
The ash value of Mrithyunjaya rasa (red&black) were 15.1% and 8.15% respectively.
Ash value in Mrithyunjaya rasa (black) is less than that of Mrithyunjaya rasa (red) , the
probable reason may be escaping of sulphur and other trace elements as oxides when we
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 146
burn the drug and difference in organic matter of the formulation.
Acid insoluble ash value:-
The acid insoluble ash value in Mrithyunjaya rasa (red&black) were negligible The
probable reason may be the absence\less percentage of silica like acid insoluble principles
in Mrithyunjaya rasa (red&black). Also signifies the genuinity of the product and
suggests it is best among all the products in terms of solubility and absorption.
Discussion on Loss on drying:
The values of loss on drying of Mrithyunjaya rasa (red&black) were 3.91%and
11.69% respectively. It is a physical test to detect the percentage of least moisture content
and hence the shelf life of the sample. The least loss on drying at 110
0
C the better will be
the drug.
Disintegration test:-
The time taken for disintegration of 5each tablets of Mrithyunjaya rasa (red&black) were
in the manner described was under normal limits.
Atomic absorption spectroscopy
The percentage of Mercury, Sulphur and borax in Mrithyunjaya rasa (Black)was 0.98%,
4.4% and 9.18% respectively and the same values in Mrithyunjaya rasa (red) were
25.01%, 17.03 %and 18% respectively. Change in the percentage of the Mercury Sulphur
and borax in Mrithyunjaya rasa (Black&red) because of change in proportions of
Mercury ,Sulphur and borax in their ingredients.
Pharmacognistical Study
Identification and authentication of drug and preparation of formulation play an
important role in this present study. An authentic formulation gives excellent result in
treatment of diseases.
In the present study Both formulations were possessed Antipyretic properties
4.Experimental results:-
Acute toxicity study was carried out in Albino rats. The procedure of single dose
was followed. Both Mrithyunjaya rasa were administered in three dosages, there was no
mortality occurred within 24hours of observation. So it was found that safe and non
toxic.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 147
Pharmacological Screening of Anti pyretic Action
Fever is explained elaborately in Modern medicine. Fever is also known as
pyrexia. fever is considered as a symptom of many diseases. Sometimes it acts as a
defense mechanism of the body. Body temperature is maintained by thermo regulation
center present at hypothalamus .It controls the body temperature by nervous feed back
mechanism by integrating the impulses obtained from the nerve endings. Pathologically
fever is induced by the pyroxenes due to infection. Pyrogens are of two types i.e.
Indigenous and exogenous. Pyrogen stimulates to produce prostaglandins. These
pyrogens increase the production of prostaglandins in hypothalamus. This prostaglandin
inhibits the thermoregulatory function and sets the thermoregulatory set point high
resulting in the condition of fever.
The study is an experimental one, mainly due to the reason that jwara is not
specifically correlated to the fever. With a specific cause but it is mainly considered to be
the rise in temperature only as the main symptom. According to Ayurvedic classics jwara
is considered as a rise in body temperature not specifically correlated to any one type.
Here yeast induced method was selected for screening Antipyretic action in albino rats.
Yeast used as pyrogens for inducing fever and then medicine was administered. Hourly
rectal temperature was recorded and analyzed statistically.
Pilot study was carried out for finding out efficacy of Brewers yeast to produce
pyrexia. Here 12 albino rats were selected and grouped into two. 1 group provided with
distilled water and 2
nd
group was administered 20% of Brewers yeast solution. Hourly
mean temperatures of albino rats were tabulated in Table No.43.
For screening experiment 42 albino rats of either sex were selected randomly and
kept under standard laboratory conditions. Only water was supplied to the rats, 18 hrs
prior to the experiment. Trial drug was prepared as per procedure mentioned in
Ayurvedic classics. Then albino rats are grouped and marked as 1, 2,C
1
,C
2
and C
3
and A
1
and A
2.
They were induced pyrexia with Brewers yeast and there after fed with test drug
in different doses and standard drug in one group. Then control group was fed with
distilled water.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 148
The initial normal rectal temperature of all the 42rats was noted. Then 20% of
Brewers yeast solution was injected at the dose of 1ml/100gm body weight
subcutaneously at the thigh region of all the rats to induce fever and kept under
observation. Symptoms like erection of fur, less active, face bent downward were
observed in all the rats. At the end of 18
th
hour rectal temperature was noted, which
confirmed that all rats were having pyrexia.
After administering the corresponding medicine to all the five groups, hourly
rectal temperature was recorded for the next 4hours.By observing the reading; it was
found that marked reduction in temperature was observed in trial drug C
2
,C
3
,A
1
andA
2
and also in standard drug group 2. There was no significant change in control group 1 and
trial drug group C
1
in half dose.
By observing the result it was found that temperature started to decrease gradually
in case C
2
trial drug in normal dose and decrease Rapidly in case of trial drug in double
dose (C
3
) ,A
1
andA
2
,. Temperature started to decline in 2-3hrs hour in case of standard
group and in control group and trial group C
1
temperature was not coming under control.
In case of C
2
and C
3
temperature came nearer to normal by 3
rd
and 2
nd
hr. In case
of C
1
temperature reduced but not came to normal. In-group 1, temperature was not
coming under control even after 4 hour. Comparison between the groups by using
statistical method.
Result
The present study is undertaken to evaluate the Jwaraghna property of
Mrithyunjaya rasa (red&black) 42 albino rats were selected and divided into 7 groups,
each contain 6 rats in groups. The results obtained are documented and tabulated as
follows.
In Control Group it is observed that temperature was 36.5
0
c at the end of 4
th
hour and not
reached normal. This shows that without medicine pyrexia cannot subside.
In Standard Group it is observed that after 2
nd
hour temperature gradually started to
decline and by the end of 3
rd
hour it reached33.6
0
c i.e., to normal temperature, This
shows significant results.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 149
In GroupC
1
it is observed that after 3
rd
hour the temperature gradually started to decline
and by the 4
th
hour it reached34.2
0
c i.e., above the normal temperature. So it can be
considered as insufficiency of dosage.
In GroupC
2
it is observed that after 2
nd
hour the temperature gradually started to decline
and by the 3
rd
hour it reached34.3
0
c i.e., to normal temperature. So it can be considered as
therapeutical dosage.
In GroupC
3
it is observed that temperature started to decrease from 2
nd
hours , after 3
rd
hours slowly attained normal level and at the end of the 4
th
hour it reached34.1
0
c which is
below normal. Albino rats were also found to be very weak. So it cannot be considered
as therapeutical dose.
In GroupA
1
it is observed that after 2
nd
hour the temperature gradually started to decline
and by the 3
rd
hour it reached33.5
0
c i.e., normal temperature. So it can be considered as
therapeutical dosage.
In GroupA
2
it is observed that after 2
nd
hour temperature started decreasing and reached
33.1
0
c i.e., normal temperature. Albino rats were also found to be very weak. So it cannot
be considered as therapeutical dose.
Table No. 55contains statistical data of all groups shows the statistically significant
results.
Table No. 56contains statistical data of all groups pair wise comparison of Temperature
with control shows statistically significant results of Group2 , C
3
,
and A
2
at 2
nd
hour
and A
1,
C
1
and C
2
at 3
rd
hour. So it can be considered as Trial drugs are having antipyretic
action.
Table No. 56contains statistical data of all groups pair wise comparison of Temperature
with Standard Shows statistically significant results of A
2
at 4
th
hour. So it can be
considered as A
2
having antipyretic action similar to standard.
Table No. 57contains statistical data of comparison between the C showing no significant
results. Table No. 58contains statistical data of comparison between the A showing no
significant results. So it can be considered as Trial drugs are having antipyretic action
irrespective of dosage.
Table No. 59contains statistical data of comparison between the C and A Groups showing
significant results.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 150
Mode of Action
On observation the pathology of disease jwara is found that the pathological
condition of jwara is due to Vikrita pitta, ama and Agnimandhya .In literary research it is
found that the trial drug Mrithyunjaya rasa (red&black)) is having property of antipyrexia
or febrifuge. It is having the ingredients which have jwaragna property. So it is found to
cure jwara effectively.
Jwaraghna dravyas are mainly having Tikta, Katu and Madhurarasas, Laghu,
Ruksha, Deepana, pachana, srotovishodhana properties. Depana, Pachana, and
srotovishodhana actions are performed by Laghu guna. In jwara Agni is impaired and
replaced. This Agni added to rasa dhatu. Along with rasadhatu it circulates all over the
body and obstructs the srotus. Due to laghu guna enters srotas and does the Amapachana
and srotoshodhana. Due to Deepana and pachana property increase the Agni, then digests
the Ama, removes the obstruction and corrects the circulation of rasadhatu.
Being tikta rasa Dravya is acts as Deepana, Pachana, Dahashamana, Vishahara,
Jwaragna, Krimihara, Pittahara and Kaphahara. Because of tikta and Kashaya rasa it can
be Sheeta veerya and katu vipaka and contributes for reducing the body temperature and
samprathi vighatana. Due to laghu and Rooksha guna it helps in Amapachana by
increasing agni and srotovishodana. By this property it acts against pyrogen and reduce
the infection. So it acts as antipyretic.
Among these two preparations of Mrithyunjaya rasa common ingredients are
Gandhaka, Vatsanabha, Tankana, Maricha, Pippali.
Vathsanabha having Katu, Tiktha, Kashaya rasa; Lahu, Rooksha, Vyavayi, Tikshna,
Vikasi Guna;Usna veerya; Madhura vipaka ; deepana, , mootrala, vedanaghna
,malarechaka, swedajanana , Pravriddhatapashamana karma. So act as jwaragna.
The antipyretic action of Vathsanabha is due to its action of dilating the blood vessels and
on sweat glands causing increased perspiration.
Pharmacology of Aconite and Aconitine-
Aconite first stimulates and later paralyses the nerves of pain, touch and temperature.
Taken internally aconite acts very notably on the circulation, the respiration and the
nervous system. The action of aconitine on the circulation is due to an initial stimulation
of the cardio-inhibitory centre in the medulla oblongata (at the root of the vagus nerves),
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 151
and later to a directly toxic influence on the nerve-ganglia and muscular fibres of the
heart itself. The respiration becomes slower owing to a paralytic action on the respiratory
centre and, in warm-blooded animals. Aconite further depresses the activity of all nerve-
terminals, the sensory being affected before the motor. In small doses it therefore tends to
relieve pain, if this be present. The cerebrum is totally unaffected by aconite,
consciousness and the intelligence remaining normal to the last. The antipyretic action
which considerable doses of aconite display is not specific, but is the result of its
influence on the circulation and respiration and of its slight diaphoretic action.
In morden medicine,formerly used in every fever, and even in the septic states that
constantly followed surgical operations in the pre-Listerian epoch, aconite is now
employed only in the earliest stage of the less serious fevers, such as acute tonsilitis,
bronchitis and, notably, laryngitis. The extreme pain and rapid swelling of the vocal cords
- with threatened obstruction to the respiration - that characterize acute laryngitis may
often be relieved by the sedative action of this drug upon the circulation.
Gandhaka having madura rasa ,amomnmochana,deepana ,vishahara, krimihara,pachana
karma.; it act as jwaragna. The antipyretic action of Gandhaka may be due to its
antibiotic ,anti-infective, anti microbial properties.
Tankana having Rooksha, Tikshna guna, deepana karma. So it act as jwaragna. Use of
Tankana in almost all Vastanabha compounds is seen in practice. This must be done as a
precautionary measure as Tankana considered to be the antitode the Vatsanabha.
Borax and boric acid check the action of saliva on starch, but, if anything, they increase
the action of the gastric juice and the pancreatic secretion. Boric acid is rapidly
eliminated in the urine, it is said to increase the urea and the quantity of urine. Large
doses increase the acidity of this fluid. It is also excreted in the saliva, sweat, and
faeces. As it is an antiseptic it has been given internally in typhoid fever and phthisis, but
with doubtful benefit. The antipyretic action of borax may be due to increasing the
amount of perspiration and causing loss of heat by evaporation.
Hingula having Tiktha, Kashaya Katu rasa Paritapanasha, agnijanana, pachana karma.
So it act as jwaragna.
Kajjali as Rasayana, as base for formulation used.
DISCUSSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 152
Dattura having Tikta, katu Lahu, Rooksha, Vyavayi, Tikshna, Vikasi Guna;Usna
veerya; pittashamaka, Pravriddhatapashamana karma it act as jwaragna
The study was done to evaluate the anti-inflammatory activity of ethanolic and ethyl
acetate extracts of root part of Datura in rats. The study was carried out by using
administered dose of 50, 100, 150, 200 mg/kg of ethanolic and ethyl acetate extracts by
orally. All extracts showed significant activity at 200 mg/kg dose. As in fever the need of
Anti-inflamatory drug , it may have been included.
Trikatu having deepana pachana karma. So it act as jwaragna.
Conclusion
CONCLUSION
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 153
CONCLUSION
From this study following conclusion can be drawn:
The trail drugs both Mrithyunjaya rasa(1&2) are explained in Jvaradhikara of
Bhaishajya Ratnavali.
These two formulations are easily preaparable and does not possess any sort of
toxic effects during its acute toxicity study Hence it is found to be a safe remedy.
Jvara is the most commonly manifested disease affecting all the individuals
irrespective of age sex etc.
The concept of Jvara is not exactly corresponding to the fever or hyper thermia
of modern concept. Even though the test drugs have been found to be
effective in reducing temperature, it cannot be consider as a drug that
cures Jvaras of various etiology. So a final result in their regard may be
obtained after a clinical evaluation of the drug in sufficiently large
population as per statistical methodology.
It is proved that the trail drugs Mrithyunjaya rasa(1&2) are having significant role
in reducing the pyrexia condition, in artificially induced pyrexia in experimental
animals.
125mg and 250mg of Mrithyunjaya rasa(1) showed significant effect in pyrexia
62.5mg dosage of Mrithyunjaya rasa(2) showed significant effect in pyrexia
So it was proved experimentally that trail drugs are efficacious in treating fever
effectively and this drug is to be further evaluated clinically to know their effect
on human beings.
Summary
SUMMARY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 154
SUMMARY
This study entitled with Comparative evaluation of antipyretic activity of two
preparations of Mrithyunjaya rasa (Bhaishajya Ratnavali) in experimentally
induced pyrexia in albino rats is presented in headings of review of literature,
materials and methods and analytical study and experimental study.
Mrithyunjaya rasa is claimed by classical texts as a universal antipyretic formulation
which is said to relieve fever of any kind. Bhaishajya Ratnavali mentions of two
preparations of Mrithyunjaya rasa which have very few ingredients, easily available in
the market, economical in cost and most of the ingredients are known to be having
antipyretic action.
The pharmaceutical study was done at Dept. of P.G Studies in Rasashastra, G.A.M.C
Bengaluru. To prepare Mrithyunjaya rasa, the Shodhana of required ingredients were
carried out at Dept. of P.G Studies in Rasashastra, G. A. M. C Bengaluru. The changes
that observed during each process of Shodhana were explained under appropriate
headings.
Evaluation of Antipyretic activity of two preparation of Mrithyunjaya rasa were
carryout at S.C.S.College of Pharmacy Harapanahalli. The results and interpretations of
experimental study were dealt under appropriate headings.
The Physico-Chemical analysis of two preparation of Mrithyunjaya rasa were
performed with help of Organoleptic characters, XRD and AAS at Dept. of P.G Studies
in Rasashastra, G. A. M. C, Bengaluru, IISc, Bengaluru and Bangalore Test House
Bengaluru serially. The results and interpretations of analytical study were dealt under
appropriate headings.
Limitations
of the study
LIMITATIONS
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 155
Limitation of study
It is a time bound research work.
Specific instrumentation and technological accreditation are taken from outside
laboratories.
Instrumental and investigatory methods for our drugs are minimum.
Modern parameters are play minor role in identifying the alteration in the drug
properties after our classical processing.
There was lack of advanced and sophisticated instruments for pharmaceutical
study.
Only rectal temperature was taken as parameter for Antipyretic activity.
Classical Jvara was evaluated in terms of pyrexia and jvarahara action as
antipyretic.
Scopes for
further study
SCOPE FOR FURTHER STUDY
COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 156
Scope for further study
Advanced analysis like N.M.R (Nuclear magnetic resonance) may be studied for
showing exact composition of Mrithyunjaya rasa.
Clinical evaluation of antipyretic activity of Mrithyunjaya rasa (Bhaishajya
Ratnavali) of both varieties may be taken up.
Clinical evaluation of antipyretic activity of Mrithyunjaya rasa (of Jvaradhikara)
may be taken up.
Comparative clinical evaluation of antipyretic activity of two preparations of
Mrithyunjaya rasa (Bhaishajya Ratnavali) may be taken up.
The Antipyretic activity of other Mrithyunjaya rasa (of Jvaradhikara) can be
assessed both experimentally and clinically may be taken up.
Pharmaco analytical study of Mrithyunjaya rasa prepared by changing Shodhana
procedure of its ingredients may be studied.
Comparative evaluation of antipyretic activity of Mrithyunjaya rasa prepared
with and without Vathsanabha may be carried out.
Comparative evaluation of antipyretic activity of Mrithyunjaya rasa prepared with
and without Dattura in 2
nd
variety.
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COMPARITIVE EVALUATION OF ANTIPYRETIC ACTIVITY OF TWO PREPARATION OF
MRITHYUNJAYA RASA IN EXPERIMENTALLY INDUCED PYREXIA IN ALBINO RATS Page 157
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174. Ibid,Chapter 4,57
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pp
175. Ibid,Chapter 5,64
th
pp
Annexure
Figure No1 Hingula before Shodhana
Figure No2 Nimbuka rasa
Figure No3 Hingula after Shodhana
Figure No4 Damaru yantra for Urdvapatana
Figure No5 Black suit after Urdvapatana
Figure No6 Unburnt Hingula after Urdvapatana
Figure No7 Parada after Urdvapatana
Figure No8 Parada with haridra
Figure No9 Parada
Figure No10 Gandhaka before Shodhana
Figure No11Gandhaka Shodhana in Dolayantra
Figure No12Gandhaka after Shodhana
Figure No13 Kajjali
Figure No14 Tankana Before Shodhana
Figure No15 Tankana after Shodhana
Figure No16 Vathsanabha before Shodhana
Figure No17 Gomutra
Figure No18 Vathsanabha after Gomutra
sthapana
Figure No19 Vathsanabha after removing of
outer covering
Figure No20 Dattura beeja before Shodhana
Figure No21 Dattura Swedana in Dolayantra
Figure No22 Dattura After Shodhana
Figure No23 Milk After Dattura Shodhana
Figure No24 Pippali
Figure No25 Maricha powder
Figure No26 Shunti powder
Figure No27 Dattura moola
Figure No28 Mrithyunjaya rasa(red)
Figure No29 Mrithyunjaya rasa(Black)
Figure No30 Mrithyunjaya rasa vati(red)
Figure No31 Mrithyunjaya rasa vati(Black)
Figure No32 Gum Acasia solution
Figure No33 Feeding needle with syringe
Figure No34 Filling of trial drug into syringe
Figure No35 Feeding to the rats
Figure No36Brewers Yeast solution
Figure No37 Injecting Brewers Yeast
solution
Figure No38 Faces bent downwards suggesting
the fatigue resulted due to raise in temperature
Figure No39 Furs erected suggesting the raise
in temperature
Figure No40 Recording the rectal temperature
Graph No-4 -Comparative Evaluation of Interventional treatment on Temperature
29
30
31
32
33
34
35
36
37
38
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
I
n
t
e
r
v
e
n
t
i
o
n
a
l
t
r
e
a
t
m
e
n
t
o
n
T
e
m
p
e
r
a
t
u
r
e
Group I Group II Group A1 Group A2
Group C1 Group C2 Group C3
Baseline Treatment period
30
31
32
33
34
35
36
37
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
P
e
r
c
e
n
t
a
g
e
s
Group I Group II
Group A1 Group A2
Group C1 Group C2
Group C3
Baseline Treatment period
Graph No-5 Pair wise comparison of Temperature
31
32
33
34
35
36
37
38
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
I
n
t
e
r
v
e
n
t
i
o
n
a
l
t
r
e
a
t
m
e
n
t
o
n
T
e
m
p
e
r
a
t
u
r
e
Group I
Group II
Baseline Treatment period
32
32.5
33
33.5
34
34.5
35
35.5
36
36.5
37
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
P
e
r
c
e
n
t
a
g
e
s
Group I
Group II
Baseline Treatment period
Graph No-6 Pair wise comparison of Temperature
29
30
31
32
33
34
35
36
37
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
I
n
t
e
r
v
e
n
t
i
o
n
a
l
t
r
e
a
t
m
e
n
t
o
n
T
e
m
p
e
r
a
t
u
r
e
Group A1
Group A2
Baseline Treatment period
31
31.5
32
32.5
33
33.5
34
34.5
35
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
P
e
r
c
e
n
t
a
g
e
s
Group A1
Group A2
Baseline Treatment period
Graph No7Pair wise comparison of Temperature
31
32
33
34
35
36
37
38
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
I
n
t
e
r
v
e
n
t
i
o
n
a
l
t
r
e
a
t
m
e
n
t
o
n
T
e
m
p
e
r
a
t
u
r
e
Group C1
Group C2
Group C3
Baseline Treatment period
32.5
33
33.5
34
34.5
35
35.5
36
36.5
37
Initial Ind. Of Pyrexia 1 hour 2 hour 3 hour 4 hour
P
e
r
c
e
n
t
a
g
e
s
Group C1
Group C2
Group C3
Baseline Treatment period