| Research Article |
Open Access |
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| Evaluation of Efficacy and Safety of Perfact Face Gel and Perfact Face
Tablets in Management of Acne |
| Nikku Yadav1*, Ajitpal Singh2, Aranee Chatterjee1 and Sateesh Belemkar1 |
| 1School of Pharmacy and Technology Management (Shirpur Campus), SVKM’s NMIMS Mumbai, Maharashtra-425 405, India |
| 2Panacea Biotec Ltd B-1Extn./A-27, MCIE, Mathura Road, New Delhi-110044, India |
| *Corresponding author: |
Dr.Nikku Yadav
H.No.564-65/20 Om Nagar, Gurgaon
Haryana-122001, India
Tel: 919372488862
E-mail: yadavnikku17@gmail.com |
|
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| Received January 25, 2011; Accepted March 07, 2011; Published March 10, 2011 |
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| Citation: Yadav N, Singh A, Chatterjee A, Belemkar S (2011) Evaluation of Efficacy
and Safety of Perfact Face Gel and Perfact Face Tablets in Management of Acne. J
Clin Exp Dermatol Res 2:118. doi:10.4172/2155-9554.1000118 |
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| Copyright: © 2011 Yadav N, et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided
the original author and source are credited. |
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| Abstract |
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| Acne is a common disease of the pilosebaceous units of the skin and topical therapy is recommended for the
management of acne with comedolytic, anti-inflammatory agents, along with antimicrobials. However, topical
application of these drugs leads to frequent adverse effects and also, there is an emergence of antibiotic resistance
by Propionibacterium acnes. Furthermore, systemic antimicrobial usage has been causally associated with various
adverse events. No simple recipe for the treatment can be provided. Treatment options vary with the stage and severity
of the disease. So now a day's physicians prefer the herboformulations containing Melaleuca alternifoli, Azadirachta
indica, Curcuma longa, Piper nigrum, Aloe vera, Citrus bergamia, Santalum album, Rosa centifolia, Carica papaya etc. than the allopathic drugs due to less or no side effects. Perfact gel is herbal formulation contains 5% of Melaleuca
alternifoli (Tea tree oil) and Perfact tablet is polyherbal formulations and contains extracts of Azadirachta indica,
Curcuma longa, and Piper nigrum, and the study was conducted to evaluate the efficacy and safety of perfect face,
Perfect face tablets and both in the management of acne. |
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| In this contest, the present work is carried out which includes Uncontrolled randomized, open labelled, multicentric
Phase III clinical trial using oral Ayurvedic multicomponent preparations with or without use of Ayurvedic dermatological
formulation in three different hospitals from 15 July 2009 to 15 Oct 2009. One hundred fifty three patients (n=153)
including 63 males and 90 females in the age group of 35-50 years were enrolled. Children below 18 years of age,
patients with preexisting systemic disease necessitating long-term medications, genetic and endocrinal disorders and
those who refused to give informed consent were excluded from the study. Pregnant and lactating women were also
excluded from the study. A baseline history was obtained in order to determine the patient's eligibility for enrolment in
the trial. Thereafter all patients underwent a clinical examination and thorough skin examination was done the subjects
are divided in to three groups. Group I received Perfect oral Tablet, Group II received dermatological gel (Perfact Face
gel) and Group III received oral tablet and dermatological gel formula. Efficacy was assessed by the ability of perfact
face gel and perfact face tablets to reduce the number of inflamed and non-inflamed lesions by using Leed's counting
method and Cardiff index method. The group III shows more 12% as compared to group II. It was concluded that group
III having more significant effect on the inflamed lesion as compared to group I and II treatment. |
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| Keywords |
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| Acne; Herbal; Clinical trial |
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| Introduction |
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| Acne vulgaris, a chronic inflammatory disorder in adolescents
consists of the pilosebaceous follicles, characterized by comedones,
papules, pustules, cysts, nodules and often scars, chiefly on face, neck
etc [1]. It is a skin condition that occurs due to the clogging of oil glands
of the skin [2]. The oil that normally lubricates the skin gets trapped in
blocked oil ducts and results in what we know as Pimples (a small skin
swellings that sometimes contain pus), Blackheads (a dark formations
on the skin due to an accumulated mixture of oil and cells in a blocked
skin pore) and Whiteheads (a small flesh-or white-colored bumps due
to skin pore blockage on the surface of skin). Sometimes it also includes
deeper skin lesions that are called Cysts (a closed sac beneath the skin
or deeper that contain fluid or semisolid substances) [3] It is more
common during teenage years but is known to happen across all age.
Adult acne is becoming increasingly popular [4]. It is a disease of the
skin which can be painful for those suffering from moderate to severe
acne [5]. Acne vulgaris mostly affects the areas of skin with the densest
population of sebaceous follicles [6] these areas include the face, the
upper part of the chest, and the back. The cause of acne is unknown.
It is presumed to be activated by androgens in genetically predisposed
individuals [7]. The earliest abnormalities in acne are: |
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| • Increased sebum production due to which the skin looks greasy
(seborrhea) |
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| • Formation of horny plugs (comedones) |
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| The general therapy in the treatment of acne vulgaris includes
oral and topical therapy employing comedolytics (Benzoyl peroxide,
Tretinoin, Azeleic acid and Isotretinoin) and antibiotics for both oral
and topical use (Tetracycline, Erythromycin, etc.) [8]. In addition to
producing bacterial resistance [9], these drugs have several side effects.
These are described for Tetracycline, Erythromycin [10], Clindamycin
[11] and Isotretinoin [12]. Although natural products are safer than
necessarily synthetic antibiotics, some patient prefer to use herbal
medicine [13]. So now a day's physicians prefer the herb formulations
containing Melaleuca alternifoli, Azadirachta indica, Curcuma longa,
Piper nigrum, Aloe vera, Citrus bergamia, Santalum album, Rosa
centifolia, Carica papaya etc [14] than the allopathic drugs due to less
or no side effects. |
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| Many hundred of plants worldwide are used in traditional medicine as treatment for Acne. Some of these have been subjected
to invitro screening but efficacy of such herbal medicine has seldom
been rigorously tested in clinical trials [15]. It is surprising that so few
clinical trials have tested the efficacy of herbal antibiotics. |
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| However, claims have not been supported with uncontrolled
clinical trials. |
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| The work reported here includes uncontrolled Phase iii clinical
trials conducted using oral multicomponent Ayurvedic preparation
with or without the use of ayurvedic dermatological formulation
developed in the company. |
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| Material and Methods |
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| Materials |
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| Perfact face gel-It contains 5% tea tree (Melaleuca alternifolia oil)
and manufactured by Panacea Biotec Ltd Larlu, Punjab India. |
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| Perfact face tablet- It contains Neem extract 200 mg, Turmeric
extract 200 mg and Piper extract 10 mg are manufactured by Panacea
Biotec Ltd Larlu, Punjab India |
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| Study design |
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| This study was an open, Randomized, uncontrolled Phase III
clinical trial conducted at three centres, B.M Hospital Ghaziabad,
Sumitra Hospital Noida and Clinic-441 Gurgaon, as per the ethical
guidelines of the Declaration of Helsinki and Good Clinical Practices
(ICH E6). The study protocol, case report forms (CRFs), regulatory
clearance documents, product-related information and informed
consent forms (English and Hindi) were submitted to the Institutional
Ethics Committee and approved by the same. |
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| Patients |
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| The study was conducted in 153 patients, 63 males and 90 females. |
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| Inclusion Criteria: One hundred and fifty three patients of both
sexes in the age group of >15 to < 50, of the out-patient from three
hospitals were included in the study. A written informed consent was
obtained from all patients. |
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| Exclusion criteria: The patients excluded in the studies were
pregnant women, breast feeding mothers and those patients who
had previous history of hypersensitivity to ayurvedic drugs, serious
hepatic or renal insufficiencies and those on treatment with other
antibiotics corticosteroids, retinoid, anticonvulsants and androgens in
the preceding four weeks. Patients excluded in the study were taking
any hormonal preparations e.g. oral contraceptive pills. Individuals
participating in new drug evaluation programme in proceeding 3
months. Patients with apparent physical or mental abnormalities.
Patients who have not taken any anti acne medication for last three
months. |
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| Clinical studies |
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| Following good clinical practices guideline, a randomized, open
label, multicentre study was conducted in three centers (Ghaziabad,
Noida and Gurgaon). One hundred fifty three patients (n=153)
including 63 males and 90 females in the age group of 35-50 years were
enrolled. They had mild to moderately acne exhibiting a minimum of
10 inflammatory lesions.i.e papules and pustules and minimum of five
non inflammatory lesions i.e. blackheads. |
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| Examination |
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| The patients were examined for the following parameters before being included in the trial. (1) Height (2) bodyweight (3) blood
pressure (4) body status (5) LFT (6) KFT (7) Hematogrm. Each patient
history was recorded for their (1) gastrointestinal motility (2)
eating habits (veg/non veg), (3) previous history of illness, (4) Seasonal
occurrence acne syndrome (5) effect of previous therapy and other
relevant details. |
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| Written informed consent was obtained from the patients after
explaining to them the purpose of conducting the trial. They were
randomized into three groups with 48,46and 47 patients in group I,
II and III respectively. They were suitably randomized. Out of total
number of patient, 10 patients dropped out of trial from respective
group. |
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| Group I received oral tablets (Perfact Tablet) containg active ingredients. |
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| Group II received dermatological gel (Perfact gel) preparation containg
active ingredients. |
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| Group III received oral tablets containg active ingredients with
dermatological gel formulation containing active ingredients. |
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| Dosage and Care Regimen |
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| After completing the clinical examination, each patients in group
I, II and III was given in the packet with 14 tablets containing active
ingriedents.Sufficient amount of topical preparation to last at least for a
week was given in the collapsible tube to each patient in group II and III
.They were explained in their local language to take one tablet twice a
day and to apply the topical preparation once daily on the effected area.
Total duration of study treatment was 4 weeks. The patient was directed
not to take any other medication and not to use any antimicrobial agent
containing soap or any cosmetics during the trial without investigator's
permission. They were asked to report to the clinic every 7th day for a
weeks. During each visit, front and bilateral 45° side facial views of every
patient were taken using a 5 megapixel 35 mm digital camera system.
After the each visit a colour picture of face was taken for counting the
lesion. For taking the photographs special instructions were followed
by investigator. After counting the lesions, scoring was given according
to Leed's counting Technique. |
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| Clinical evaluation |
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| A single physician recorded all the clinical observations using
assessment scale ((Leeds count [16] and Cardiff Acne disability Index
[17]).In this patient overall change in facial acne compared with his
or her appearance at the beginning of study was made on the four
point scale ranging from excellent to poor response. The first overall
assessment of the acne severity in a particular area (grade between 0
to10) is accurate, reproducible, rapid and suitable for use in routine
clinic. |
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| Statistical analysis was done using paired t-test and Pearson's
coefficient of correlation. Mean values (+/- standard deviation) will
be calculated, as well as variations of the parameters relative to pre
treatment values (expressed in %). Two-tailed paired Student's t test
will be used to determine the significance of the results (comparisons
between pre-treatment, after 2 weeks and after 4 weeks of treatment)
for the parameters determined with the level of significance being set
at 5%.The minimum level of significance was fixed at 95% confidence
limit and a 2-sided p value of <0.05 was considered significant. The
values are expressed in the sequence as: mean score (M) at 2nd and 4th
week, standard deviation (SD) at baseline, 2nd and 4th week, standard
error of mean (SEM) at 2nd and 4th week lower 95% confidence interval
(CI) of mean at 2nd and 4th week, upper 95% confidence interval (CI) of
mean at 2nd and 4th week, squared R value, p value, significant (S). In all
graphs, the baseline value is 0.00. |
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| Results |
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| Demographic distribution of patient included in the study is shown
in Table 1 and 2. In all 141 patients completed the study and there were
twelve dropouts. None of patients were non-compliant with respect to
drug administration and application. Total non inflamed lesions i.e. total number of white heads and black heads gradually reduced during
the treatment and the reduction was statistically significant at 2nd and 4th week of therapy as compared to total non inflamed lesions on the day
of screening of subjects. |
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| A decrease in total number of white heads in the subjects was
observed that was statistically significant at week 2 and week 4 when
compared to the white heads at week 0. (Figure1a), (Figure 2) Table 3 showing the change in total no .of lesions with treatment with perfact
tablets. |
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| The percentage improvement in blackheads was found to be similar
in all the groups. Group I shows the improvement from 47.5% at week
2 to 74.11% at week 4. Group II shows the improvement from 48.17 %
at week 2 to 78.3% at week 4.In case of Group III, similar improvement
was observed. The difference at week 2 and 4 was found to be statistically
significant when compared to mean number of blackheads at the start of
therapy (Figure b),(Figure 3) The improvement of Papules was 73.22%,
71.4% and 75.8% at week 4 in Group I, II, and III respectively (Figure
4a), (Figure 5). The Group II shows less improvement as compare to
other group. The difference at week 2 and week 4 was found to be
significant when compared to mean number of inflamed lesion at the
start of therapy. The improvement of Pustules was 86.35.0%, 86.40% and
82.70% at week 4 in Group I, II, and III respectively (Figure 4b), (Figure
6). It is observed that Cyst showed improvement of 2.2%, 8.8% and
2.9% after 4 weeks of treatment in Group I, II and III respectively (Figure 7a). The improvement of nodules was 31.9%, 13.00% and 41.2% at
week 4 in Group I, II, and III respectively (Figure 7b), (Figure 8). There
was no serious adverse event reported during the entire course of study. |
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Table 1: Demographic data of all the subjects participating in clinical trial. |
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Table 2: Presence of Acne with Time. |
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Table 3: showing the change in total no .of lesions with treatment with perfact
tablets. |
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Table 4: showing the change in total no. of lesions with treatment with perfact gel. |
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Table 5: showing the change in total no. of lesions with treatment with perfact gel
& perfact tablets. |
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Table 6:Cardiff Acne disability score for all Treatment Groups. |
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Figure 1: Change in no. of noninflamed lesions with time with all treatment
groups (a) whiteheads (b) blackheads (n=48) *P<0.05 tablet, # P<0.05 gel, @
P<0.05 tablet+gel. |
|
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Figure 2: Shows the Presence of whiteheds before the treatment and after
the treatment in all the treatment group.(1.a) Group I before treatment (1.b)
Group II after treatment, (2.a) Group II before treatment (2.b) Group II after
treatment,(3.a)Group III before treatment (3.b)Group III after treatment. |
|
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Figure 3: Shows the Presence of Blackheads before the treatment and after
the treatment in all the treatment group.(1.a) Group I before treatment (1.b)
Group II after treatment, (2.a) Group II before treatment (2.b) Group II after
treatment,(3.a)Group III before treatment (3.b)Group III after treatment. |
|
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Figure 4: Change in no. of inflamed lesions with time with all treatment
groups (a) Papules (b) Pustules (n=48) * P<0.05 tablet, # P<0.05 gel, @P<0.05
tablet+gel. |
|
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Figure 5: Shows the Presence of Papules before the treatment and after the
treatment in all the treatment group.(1.a) Group I before treatment (1.b)
Group II after treatment, (2.a) Group II before treatment (2.b) Group II after
treatment,(3.a)Group III before treatment (3.b)Group III after treatment. |
|
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Figure 6: Shows the Presence of Pustules before the treatment and after
the treatment in all the treatment group.(1.a) Group I before treatment (1.b)
Group II after treatment, (2.a) Group II before treatment (2.b) Group II after
treatment,(3.a)Group III before treatment (3.b)Group III after treatment. |
|
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Figure 7: Change in no. of deep lesions with time with all treatment groups
(a) Cysts (b) Nodules (n=48) *P<0.05 tablet, # P<0.05 gel, @P<0.05 tablet+gel. |
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Figure 8: Shows the Presence of Nodules before the treatment and after
the treatment in all the treatment group (1.a) Group I before treatment (1.b)
Group II after treatment, (2.a) Group II before treatment (2.b) Group II after
treatment,(3.a)Group III before treatment (3.b)Group III after treatment. |
|
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| Discussion |
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| As per the guidelines of The American Academy of Dermatology,
primary acne vulgaris is classified into mild, moderate and severe grades. Mild acne is characterized by the presence of few to several papules
and pustules (without nodules). Patients with moderate acne have too
many papules and pustules (along with a few to several nodules) and
with severe acne, patients have numerous or extensive papules and
pustules (as well as many nodules). Acne is also classified by lesion
type as comedonal, papulopustular and nodulocystic [18]. Tea tree oil
(an essential oil of the native Australian tree Melaleuca alternifolia) has
been used as a topical antiseptic agent [19]. The studies have shown that
tea tree oil can be used in treatment of acne vulgaris [20]. |
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| Infact, topical application of 5% tea tree oil has been shown to be
equivalent to 5% Benzoyl peroxide in efficacy. Moreover, the use of tea
tree oil is associated with much lesser side effects [15]. |
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| Azadirachta indica contains many essential oils that have
antipyretic and antihelmintic properties [21]. It helps in controling
the biliary secretion and purifies the blood. It is a good remedy for
splenic enlargement [22]. Some Indian herbs including Curcuma
longa, Azadirachta indica have been shown to have anti-inflammatory
effect by suppressing the Propionibacterium acnes [23] induced ROS
(reactive oxygen species) and pro-inflammatory cytokines [1,23]. Due
to this pharmacological activity, these herboformulation are may be
used in the treatment of Acne. |
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| This direct anti-inflammatory property is considered to be the
basis for the clinical effect of these herbs in treating acne. These herbs
act as in the similar manner as the Azelaic acid, which is use in the
treatment of Acne as oral antibiotic [4]. Topical and oral preparations
of Indian herbs (Maelaleuca alerternifolia, Curcuma longa, Azadirachta
indica and Piper nigrum) are efficacious in treatment of Acne [24].
The
combination of use of internal and external preparation showed better
efficacy as compared to the use of oral formulation alone. |
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| All the three treatment arms demonstrated improvement in both non-inflamed and inflamed lesions including superficial and deep ones.
For non inflamed lesion (superficial lesions) the improvement with
perfact face tablets and perfact face tablets +gel was almost identical.
The improved observed with perfact face gel alone was slightly lower
at the end of 4 weeks of therapy as compared to other arms (Figure 8). |
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| The difference in the improvement in inflamed lesions (papules and pustules) was slightly more evident between the treatment arms
containing tablets (with or without gel) and gel only. There was a
difference of about 9.21% in the improvement percentage of treatment
arms containing tablet and treatment arm without tablet at end of 4
weeks of therapy. The group I shows the significant Improvement in the
inflamed lesions as compared to group II. The group III shows more
effect (12%) as compared to group II. It was concluded that group III
having more significant effect on the inflamed lesion as compared to
group I and II treatment (Figure 9). |
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| The maximum disparity in acne improvement is observed in
deep inflammatory lesions. It was observed that the difference in
acne improvement in treatment arm with only perfact face gel was
17% as compared to subjects in treatment arm with only perfact face
tablet. This difference was further elated to 20% when comparing with
subjects in treatment arm containing perfact face tablets and gel. All
the three treatments viz. Perfact face acne tablets, Perfact face acne
gel and Perfact face acne tablets & gel showed statistically significant
reduction in total inflamed lesions i.e. papules and pustules at 2nd
and 4th week of therapy as compared to total inflamed lesions on the
day of screening of subjects (Figure 10). Cardiff acne disability index
was found significantly improved at the end of the therapy with all
the three treatments viz. Perfact face acne tablets, Perfact face acne gel
and Perfact face acne tablets & gel. No clinically significant change in
any of the biochemical parameter is observed in any of the treatment
group. There was no difference among the three treatment arms. It was
concluded that four weeks of therapy with Perfact face acne tablets and
Perfact face acne gel has no effect on hematological profile of the subject
including liver and kidney function tests. |
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Figure 9: Comparative evaluation of non inflamed lesion in all the three
treatment group. |
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Figure 10: Comparative evaluation of inflamed lesion in all the three treatment
group. |
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Figure 11: Comparative evaluation of deep lesion in all the three treatment
group. |
|
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| Conclusion |
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| Data reported in this study clearly show that the improvement
observed with Perfact face acne gel alone was slightly lower at the end
of 4 weeks of therapy as compared to when given along with Perfact oral
tablets or when Perfact oral tablets given alone. The efficacy of group
III treatment was more as compare to group I and II treatment. The
safety parameters remained same before and after the therapy. There
were no deaths or serious adverse events. The interim result of the
study indicates that perfact face oral tablet and perfact face gel were
well tolerated. |
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| Acknowledgement |
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| The authors are thankful to Panacea Biotec Ltd, New Delhi, India and School
of Pharmacy Technology and Management NMIMS, Shirpur Campus, Maharashtra
for providing the required facilities, guidance and support. |
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