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Clinical efficacy of polyherbal formulation Eezpain spray for muscular pain relief

Authors:
  • GlaxoSmithKline, Pakista
  • Herbion Naturals

Abstract and Figures

The topical herbal formulation Eezpain spray consisting of natural ingredients that have been clinically proved for its analgesic and anti-inflammatory activity. The designed formulation on application knee and wrist joints, back of neck and shoulder, forearms and lower back exhibited significant efficacy. A total of 20 subjects both male and female applied Eezpain spray consisting of Gaultheria oil, Eucalyptus oil, Turpentine oil, Clove Oil, Menthol and Camphor. All the active materials are cited that these have analgesic activity in myalgia and neuralgia. The study design was prospective and opens as pilot study followed the inclusion and exclusion criteria. All the sign and symptoms were noted at baseline and at the end of 14 days treatment performance was evaluated. The statistical analysis was done by using Microsoft Excel2007 and SPSS version 18.0. It is concluded that Eezpain spray has shown efficacy in mild to moderate cases on applying locally to the affected parts to relieve pain from different ailments.
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Pak. J. Pharm. Sci., Vol.28, No.1, January 2015, pp.43-47 43
Clinical efficacy of polyherbal formulation Eezpain
spray for muscular pain relief
Allah Nawaz, Zeeshan Ahmed Sheikh, Majid Feroz, Kamran Alam, Halima Nazar
and Khan Usmanghani
Department of Research and Development, Herbion Pakistan (Pvt.) Limited,
Plot 30, Sector 28, Korangi Industrial Area, Karachi, Pakistan
Faculty of Eastern Medicine, Hamdard University, Karachi, Pakistan
Abstract: The topical herbal formulation Eezpain spray consisting of natural ingredients that have been clinically proved
for its analgesic and anti-inflammatory activity. The designed formulation on application knee and wrist joints, back of
neck and shoulder, forearms and lower back exhibited significant efficacy. A total of 20 subjects both male and female
applied Eezpain spray consisting of Gaultheria oil, Eucalyptus oil, Turpentine oil, Clove Oil, Menthol and Camphor. All
the active materials are cited that these have analgesic activity in myalgia and neuralgia. The study design was
prospective and opens as pilot study followed the inclusion and exclusion criteria. All the sign and symptoms were noted
at baseline and at the end of 14 days treatment performance was evaluated. The statistical analysis was done by using
Microsoft Excel2007 and SPSS version 18.0. It is concluded that Eezpain spray has shown efficacy in mild to moderate
cases on applying locally to the affected parts to relieve pain from different ailments.
Keywords: Analgesic, anti-inflammatory, myalgia, natural.
INTRODUCTION
In alternative medicine the essential oils are mostly used
as analgesic and anti-inflammatory remedies. It is
described that some compounds that confer the effects of
essential oils and the molecular mechanisms are largely
unknown for example, linalool, a monoterpene compound
commonly found as a major component of several
essential oils has seen reported to produce anti-
nociception in two different pain models in mice although
the mechanism of its analgesic effects is unknown (Peana
AT et al., 2003). Menthol, the main ingredient of Mentha
piperita L, is used for pain relief in daily life due to anti-
nociception effects to some extent (Proudfoot CJ et al.,
2006 and Galeotti N et al., 2002). Even though high doses
of menthol caused sensory irritation (Green BG, 1992)
because it acts as an activator of chemical noci-sensor
[TRPA1/Transient receptor potential (TRP)] in humans
(Karashima Y et al., 2007). Camphor, is also known to
exert the analgesic effects due to inhibition of TRPA1
(Xu H et al., 2005) and activation of thermo sensitive
receptor (TRPM8) (Vogt-Eisele AK et al., 2007).
However, camphor is not suited for use as an analgesic
compound because it causes a warm and hot sensation
(Green BG, 1990), probably through TRPV1 activation
(Xu H et al., 2005). Herbion newly designed Eezpain
spray is soothing and emollient effect that provides relief
from localized muscular pain and joint pain on applying
externally. It contains Gaultheria oil, Eucalyptus oil,
Turpentine oil, Clove Oil, Menthol and Camphor along
with excipients to formulate the dosage form as spray.
Aim of study
This study was aimed to evaluate the clinical efficacy and
safety of Eezpain spray for the treatment of muscular pain
and joint pain.
Methodology
Unit Composition of Eezpain Spray
The unit composition of Eezpain spray consist of the
following ingredients and quantity mentioned herewith in
each 100ml, as Mentha piperata - Menthol crystals,
1.500g; Mentha piperata- Menthol crystals, 0.500g;
Gaultheria procumbens (Gaultheria oil), 3.400ml;
Eucalyptus globules (Eucalyptus oil); Turpentine Oil, 1-
135ml; Syzgium camphora (Clove oil), 0470ml; whereas
excipients added are Propylene Glycol, 60.385gm; Tween
20, 5.0000gm; Polyethylene Glycol PEG 400, 15.000ml;
IPA, 10.000ml; Benzyl alcohol, 0-4000ml.
Stability testing on Eezpain spray
The stability testing of Eezpain spray is mentioned as
mentioned as under: Reason for stability being the new
product (Pet bottle with plastic cap); stability condition:
Accelerated 40oC±2, RH 75%±5, long term 30oC±2, RH
65%±5, testing frequency: Accelerated: Initial, 3 & 6 long
term: Initial, 3, 6, 9, 12, 18, 24, test performed:
Appearance, pH, density and microbiological purity,
Results: 12 months (accelerated & long term) results
found satisfactory.
Study design
This study was prospective, open, non-comparative
clinical trial. Clinical trial proforma, study protocol and
product related information and informed consent forms
*Corresponding author: e-mail: dr.anawaz786@gmail.com
Clinical efficacy of polyherbal formulation Eezpain spray for muscular pain relief
Pak. J. Pharm. Sci., Vol.28, No.1, January 2015, pp.43-47
44
were submitted to the Research and Development
Department of Herbion Pakistan (Pvt.) Limited.
Inclusion criteria
A total of 20 subjects of either sex who were diagnosed
and categorized as suffering from pain into group 1 and
group 2 were included in this study. Group 1 includes
minor aches i.e. backache, sprains, neck pain, shoulder
pain and muscular pain of limbs while group 2 includes
chronic disorder i.e. rheumatoid arthritis, osteoarthritis,
weight related joint disorder etc.
Graph 1(A): Age distribution of enrolled patients
Graph 1(B): Sex distribution of enrolled patients
Exclusion criteria
The patients with chronic skin problems, hypersensitivity
and any other chronic ailments except group 1 and group
2 complaints.
Safety parameters
Inhaled or topical use of essential oils is much safer than
oral use. However, allergic reactions to inhaled or topical
plant fragrances are not uncommon. The systemic toxicity
can result from ingestion or topical application at higher
than recommended doses (Darben et al., 1998).
Table 1: Sex and Age distribution of the respondent
S. No. Respondents Age Gender
1 Respondent 65 Female
2 Respondent 56 Female
3 Respondent 61 Female
4 Respondent 50 Male
5 Respondent 40 Female
6 Respondent 54 Male
7 Respondent 30 Female
8 Respondent 34 Male
9 Respondent 39 Female
10 Respondent 42 Male
11 Respondent 35 Female
12 Respondent 30 Female
13 Respondent 50 Male
14 Respondent 46 Female
15 Respondent 35 Male
16 Respondent 31 Female
17 Respondent 56 Male
18 Respondent 55 Female
19 Respondent 60 Male
20 Respondent 62 Male
Work plan
At first the patients suffering from complaints of muscular
pain or joint pain were screened out and initial history
was taken on prescribed history sheet. The selected
subjects were enrolled for clinical trial after taking
informed consent from the patients. The patients were
advised to externally apply Eezpain spray herbal
formulation gently on affected part 2-3 times daily for 2-
14 days with special is instruction i. e. avoid contact with
eyes, should not apply to facial areas and do not bandage
tightly or use with heated pads. The Eezpain spray has
been designed only symptomatic improvement and the
patients were examined at each follow up visit.
Thoroughly examined the patient at every follow up visit
and compare the level of improvement from baseline
symptoms. The efficacy of Eezpain spray was assessed by
mean of improvement in symptoms. We used generally
three parameter to estimate the efficacy as excellent
indicate (upto 70%), average indicate 50%) and no effect
showed that there was no improvement. At the end of 14
days, the overall performance were evaluated and
compared with baseline. Statistical evaluation of the
collected data was done by using SPPS version 18.0 and
Microsoft excels 2007. Chi-square test and cross
tabulation were used for evaluation of significance of
results. In this case chi square value less than 0.5 indicate
Allah Nawaz et al
Pak. J. Pharm. Sci., Vol.28, No.1, January 2015, pp.43-47 45
significance of the Eezpain spray. The study was
conducted at Sohail Memorial Hospital, Landhi, Karachi
in outpatient ward.
RESULTS
The clinical efficacy of herbal formulation Eezpain spray
in the management of muscular pain (myalgia) and joint
pain (Osteaoartritis and knee joint inflammation)
indicated that Eezpain has statistically significant results
in reducing the pain, inflammation, tenderness and
provide calming effects also.
It was a pilot study conducted on 20 patients. The age
limit was 30-70 years and duration was 10 day to 14 days
only. The distribution of patients according to age and sex
is given below in table 1 and Graph 1 and 2.
The overall efficacy of Eezpain spray is given in table 2
and 3. None of the patients complained or exhibited any
adverse effects. The Eezpain spray has shown good
efficacy in-group 1 and average efficacy in-group 2.
In this table the data was analyzed by using Cross
tabulation in SPSS version 18.0 software and compared
the efficacy of Eezpain spray by mode of application per
day. It has proved that by applying Eezpain spray three
times daily, its efficacy is maximum for curing the pain
symptoms. No allergic reactions or side effects were
noted on the use of Eezpain spray by the participants.
DISCUSSION
The application of Eezpain spray on affected part
provides instant relief may be due to synergistic effects o
fall active ingredients. The essential oil of leaves of
Gaultheria provides quick relief from muscular pain when
applied externally (Khare CP, 2004; Chopra RN et al,
1956; Ma XJ et al., 2001). Another ingredient of Eezpain
spray, camphor that is absorbed readily through skin and
it provides feeling effects of cooling and good anesthetic
and very effective for local anesthesia. The excellent
feature of camphor is that it causes numbness of sensory
nerves and affected area of application (Majid MH, 2010).
When camphor applied to external skin, it numbs the
nerve endings and these nerve endings then cannot
transmit pain sensation (Bown D., 1995).
Turpentine has also shown a reduction in muscular pain in
lumbar region and found to have an emergent effect to
improve blood circulation and neuropathic pain reduction
(Davydova et al., 1998; Pushkareva, 1978). Menthol in
Mentha piperita may provide instant relief from pain and
provide soothing and cooling effect as it was documented
that it has analgesic activity in myalgia and neuralgia
(Khare CP, 2004; Haas M, 2004). As Pinus roxburghii
sergeant has also shown the musculorelaxant and
analgesic activity due to its oleoresin i.e. alpha and beta
pinene constituents (Khare CP, 2004; Chopra RN et al,
1956).
Table 2: Improvement in signs and symptoms
Effects Results S.
No. Presenting Illness
Severity
of Disease Duration of
Treatment Excellent Satisfactory No Effect
1. Knee joint pain Mild 14 Days 1 0 0
2. Back ache Mild 12 Days 0 1 0
3. Cervical pain Severe 10 Days 0 1 0
4. Back ache Moderate 12 Days 1 0 0
5. Ankle joint pain Moderate 15 Days 0 0 1
6. Ankle Injury Severe 10 Days 0 0 1
7. Knee injury
inflammation Moderate 14 Days 0 0 0
8. Back ache Moderate 15 Days 0 1 0
9. Osteo-Arthritis Moderate 14 Days 0 1 0
10. Back ache Mild 14 Days 1 0 0
11. Cervical pain Moderate 14 Days 0 1 0
12. Back ache Severe 12 Days 0 0 1
13. Back ache Moderate 15 Days 0 1 0
14. Ankle joint pain Moderate 12 Days 0 1 0
15. Ankle Injury Severe 10 Days 0 0 1
16. Knee injury
inflammation Moderate 14 Days 1 0 0
17. Back ache Severe 12 Days 0 0 1
18. Osteo-Arthritis Moderate 14 days 0 1 0
19. Back ache Moderate 14 Days 0 1 0
20. Joint Pain Mild 14 Days 1 0 0
Found efficacious
in mild to moderate
cases of pains and
inflammation
Clinical efficacy of polyherbal formulation Eezpain spray for muscular pain relief
Pak. J. Pharm. Sci., Vol.28, No.1, January 2015, pp.43-47
46
The previous study described that the analgesic effects of
the essential oil of Syzygium aromaticum, which was seen
may be due to euginol. It was also confirmed in another
study that anti-nociceptive activity of eugenol against
chemical (acetic acid tests), as well thermal stimuli. They
also suggested that the eugenol predominantly inhibits the
peripheral pain mechanism (Daniel AN et al., 2009;
Kurian R et al., 2006). It is found that significant pH i.e.
pH <0.5 in case of Eezapin spray calculated by using Chi
square test SPSS version 18.0. Overall the results
obtained of Eezpain spray on different types of pain
ailments gave mild to moderate improvements in pain and
these can be correlated and comparable with the earlier
studies. The different constituents and mechanism are
highlighted in their role to reduce pain as the overall
effects.
CONCLUSION
It is concluded that Eezpain spray has shown efficacy in
mild to moderate cases on applying on affected parts.
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Table 3: Level of improvement cross tabulation
Application per day * Level of Improvement Cross tabulation
Level of Improvement
Mild
Improvement Moderate
Improvement Total
Count 4 4 8
% within Application per day 50.0% 50.0% 100.0%
% within Level of Improvement 44.4% 36.4% 40.0%
Once daily
% of Total 20.0% 20.0% 40.0%
Count 5 5 10
% within Application per day 50.0% 50.0% 100.0%
% within Level of Improvement 55.6% 45.5% 50.0%
Twice
daily % of Total 25.0% 25.0% 50.0%
Count 0 2 2
% within Application per day .0% 100.0% 100.0%
% within Level of Improvement .0% 18.2% 10.0%
Application per
day
Three
times in a
day % of Total .0% 10.0% 10.0%
Count 9 11 20
% within Application per day 45.0% 55.0% 100.0%
% within Level of Improvement 100.0% 100.0% 100.0%
Total
% of Total 45.0% 55.0% 100.0%
Allah Nawaz et al
Pak. J. Pharm. Sci., Vol.28, No.1, January 2015, pp.43-47 47
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Eugenia caryophyllata, popular name "clove", is grown naturally in Indonesia and cultivated in many parts of the world, including Brazil. Clove is used in cooking, food processing, pharmacy; perfumery, cosmetics and the clove oil (eugenol) have been used in folk medicine for manifold conditions include use in dental care, as an antiseptic and analgesic. The objective of this study was evaluated the anti-inflammatory and antinociceptive activity of eugenol used for dentistry purposes following oral administration in animal models in vivo. The anti-inflammatory activity of eugenol was evaluated by inflammatory exudates volume and leukocytes migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. The antinociceptive activity was evaluated using the acetic acid-induced writhing and hot-plate tests in mice. Eugenol (200 and 400 mg/kg) reduced the volume of pleural exudates without changing the total blood leukocyte counts. At dose of 200 mg/kg, eugenol significantly inhibited carrageenan-induced edema, 2-4 h after injection of the flogistic agent. In the hot-plate test, eugenol administration (100 mg/kg) showed unremarkable activity against the time-to-discomfort reaction, recorded as response latency, which is blocked by meperidine. Eugenol at doses of 50, 75 and 100 mg/kg had a significant antinociceptive effect in the test of acetic-acid-induced abdominal writhing, compared to the control animals. The data suggest that eugenol possesses anti-inflammatory and peripheral antinociceptive activities.
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