Evaluation of efficacy and safety of Acne-N-Pimple cream in acne by jizhen1947

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									 Evaluation of efficacy and safety of Acne-N-Pimple cream in acne vulgaris
                                   G. Ravichandran, MD, DD, M. Derm.1,
 V. Shivaram Bharadwaj, Dip. N.B. (Surg.), FRCS (Edin.), FRCS (Plastic Surg.)2 and S.A. Kolhapure, MD3*
                   1
                     Consultant dermatologist, 2Consultant Plastic & Reconstructive Surgeon
                                 Apollo Hospitals, Chennai, Tamil Nadu, India
           3
             Senior Medical Advisor, R&D Center, The Himalaya Drug Company, Bangalore, India

                                        [*Corresponding author]

                                  [The Antiseptic (2004): 101(12), 249]

Abstract
Acne vulgaris is a common skin disorder and the available drugs have been shown to be
associated with specific limitations. The present study was planned to evaluate the efficacy
and safety of “Acne-N-Pimple Cream” in the management of acne vulgaris.

This study was a prospective, open, non-comparative, phase III clinical trial and a total of 26
patients, who were diagnosed as suffering from acne vulgaris were included in the study.
Children below 18 years of age, patients with pre-existing systemic disease necessitating
long-term medication, genetic and endocrinal disorders, and those who refused to give
informed consent were excluded from the study. Pregnant the lactating women were also
excluded from the study. A baseline history was obtained, which included personal data, a
description of symptoms and details of past medical history and thereafter all patients
underwent a clinical examination and thorough skin examination. All the patients were
advised to apply the “Acne-N-Pimple Cream” on the affected area, twice daily for a period of
6 weeks. All the patients were followed up for a period of 6 weeks. The predefined primary
efficacy endpoints were reduction in number of blackheads and whiteheads, inflamed pustules
and overall inflammation along with an increase in exfoliation, overall moisturizing and
soothing effect, and healing without scar formation. The predefined secondary safety
endpoints were incidence of adverse events and compliance to the drug treatment.

This study observed significant reduction in the number of blackheads and whiteheads, in
number of inflamed pustules and overall inflammation. Similarly there was enhanced
exfoliation, moisturizing and soothing effect along-with significant improvement in healing
without scar formation. There were no clinically significant short- and long-term adverse
reactions, during the entire period of the study and excellent patient compliance to “Acne-N-
Pimple Cream” was observed. The excellent results obtained might be due to the antioxidant,
anti-inflammatory, antiandrogenic and antimicrobial properties of the ingredients. Therefore,
it may be concluded that “Acne-N-Pimple Cream” is clinically effective and safe in the
management of acne vulgaris.

Introduction
Acne vulgaris is a common skin disorder, affecting virtually all adolescents and adults at
some time in their lives. Although the overall health is not impaired, acne is not a trivial
disease, as it can produce cutaneous and emotional scars that last a lifetime.1-3 Numerous
psychological problems stem from acne, some even resulting in decreased employability in
adulthood.4

The etiology of acne is multifactorial and according to the severity of inflammation, acne is
classified into purely comedonal (non-inflammatory acne), mildly papular, scarring papular
and scarring nodular acne. Clinically, the peak incidence of acne is evident during the teen


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years, but a significant chunk of men and women between 20-40 years of age also suffer from
acne vulgaris.5,6

Topical therapy is recommended for the management of acne vulgaris, especially for patients
with non-inflammatory comedones and mild to moderate inflammatory acne. Comedolytic
and anti-inflammatory agents along with antimicrobials are generally preferred in topical
treatment of acne. But, the available drugs used for topical and systemic management of acne,
have been shown to be associated with specific limitations. For example, topical application
of tretinoin leads to dermal adverse reactions (erythema, peeling and burning of the skin).
During the past few decades many reports have documented an emergence of antibiotic
resistance by Propionibacterium acnes during the treatment of acne7-9 and systemic
antimicrobials have been causally associated with various short- and long-term adverse
effects).10

“Acne-N-Pimple Cream” is a polyherbal formulation recommended for the management of
acne vulgaris and it contains the powders of Lenus culinaris and Alum, with extracts of
Salmalia malabarica, Vitex negundo and Aloe barbadensis. The present study was planned to
evaluate the efficacy and safety of “Acne-N-Pimple Cream” in the management of acne
vulgaris.

Study aim
This study was planned to evaluate the clinical efficacy and safety (short- and long-term) of
“Acne-N-Pimple Cream” in the management of acne vulgaris.

Study design
This study was a prospective, open, non-comparative, phase III clinical trial, conducted at the
department of Dermatology of The Apollo Hospitals, Chennai, India, as per the ethical
guidelines of Declaration of Helsinki, from June to September 2004. The study protocol, case
report forms, regulatory clearance documents, product related information and informed
consent form (in Tamil and English) were submitted to the “Institutional Ethics Committee”
and were approved by the same.

Materials and methods
Inclusion criteria
A total of 26 patients, who were diagnosed as suffering from Acne vulgaris, and who were
willing to give informed consent were included in the study.

Exclusion criteria
Children below eighteen years of age, patients with preexisting systemic disease necessitating
long-term medication, genetic and endocrinal disorders, and those who refused to give
informed consent were excluded from the study. Pregnant the lactating women were also
excluded from the study.

Study procedure
A baseline history was obtained in order to determine the patient’s eligibility for enrolment in
the trial. The baseline assessment included personal data, a description of symptoms and
details of past medical history (family history of acne, history of possible exacerbating
factor/s, etc.). Thereafter, all the patients underwent a clinical examination and thorough skin
examination was done for presence of black and white heads, inflamed papules and pustules,



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and cysts and nodules. All the patients were advised to apply the “Acne-N-Pimple Cream” on
the affected area, twice daily for a period of 6 weeks.

Follow-up and monitoring
All the patients were followed up for a period of 6 weeks and at each weekly follow-up visit,
the improvement in the acne lesions was evaluated. At the end of the 6th week, the overall
performance of the “Acne-N-Pimple Cream” was evaluated.

Primary and secondary endpoints
The predefined primary outcome measures were reduction in the number of blackheads and
whiteheads, inflamed pustules and overall inflammation along with an increase in exfoliation,
overall moisturizing and soothing effect and healing without scar formation. The predefined
secondary outcome measures were incidence of adverse events and compliance to the drug
treatment.

Adverse events
All local and systemic adverse events, reported or observed by patients were recorded along
with information about severity, time of onset, duration and action taken regarding the study
drug. Relation of adverse events to study medication was predefined as “Unrelated” (a
reaction that does not follow a reasonable temporal sequence from the time of administration
of the drug), “Possible” (follows a known response pattern to the suspected drug, but could
have been produced by the patient’s clinical state or other modes of therapy administered to
the patient), and “Probable” (follows a known response pattern to the suspected drug that
could not be reasonably explained by the known characteristics of the patient’s clinical state).
   Patients were allowed to voluntarily withdraw from the study, if they had experienced
serious discomfort during the study or sustained serious clinical events requiring specific
treatment. For patients withdrawing from the study, efforts were made to ascertain the reason
for dropout. Non-compliance (defined as failure to take less than 80% of the medication) was
not regarded as treatment failure, and reasons for non-compliance were noted.

Results
A total of 26 patients were
included in this study and the
age range was 20-30 years.
There was a significant
reduction in number of
blackheads and whiteheads,
from 2nd week onwards, when
compared to the baseline.
There was significant reduction
in number of inflamed pustules,
when compared to the baseline
and the overall inflammation,
as judged clinically was also
significantly improved when
compared to the baseline.
Similarly, exfoliation also
showed               significant   Figure 1: Response to drug treatment (Acne-N-Pimple cream)
improvement when compared
to the baseline.


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There was enhanced moisturizing effect from the 2nd week onwards and in addition, the
soothing effect was also improved when compared to the baseline. There was a significant
improvement in healing without scar formation.

The overall response to the drug treatment also recorded a significant improvement from the
2nd week onwards and 14 (54%) patients graded the treatment as good, 10 (38%) patients
graded the treatment as very good, while 1 subject (4%) graded the treatment as excellent
(Figure 1).

There were no clinically significant short- and long-term adverse reactions (either reported by
the patients or observed by the investigators), during the entire period of the study and
excellent patient compliance to “Acne-N-Pimple Cream” was observed.

Discussion
Acne vulgaris is a chronic inflammatory disease of the pilosebaceous units. The etiologic
factors include increased sebum production, ductal hyperkeratosis, abnormality of the
microbial flora within the pilosebaceous unit, and chemomediators of inflammation. The
dermal inflammation is not due to presence of bacteria, but from biologically active
chemomediators produced by P. acnes and the microenvironment within the pilosebaceous
unit, is probably more important than the absolute number of P. acnes organisms. Indeed, the
major role of the sebaceous gland appears to be supplying nutrients needed by P. acnes and
moreover, the microbiologic principle of biofilms appears to be applicable to P. acnes in
acne.11

The recent demonstration that the ‘peroxisome proliferator activated receptors’ (whose natural
ligands are polyunsaturated fatty acids and theirs oxidation products), have a central role in
the induction of acne, has indicated new links between free radicals and skin inflammation.12
Further, it has been shown that androgens also play an important role in the pathogenesis of
acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly
through follicular hyperkeratinization.13

Acne is associated with a greater psychological burden than a variety of other disparate
chronic disorders. Various studies have demonstrated that patients with acne vulgaris suffer
psychological aberrations like depression, anxiety, psychosomatic symptoms (pain and
discomfort), embarrassment and social phobia. Effective treatment of acne vulgaris is
accompanied by improvements in self-esteem, social assertiveness and self-confidence.14

This study observed significant reduction in the number of blackheads and whiteheads, in the
number of inflamed pustules and overall inflammation. Similarly, there was enhanced
exfoliation, moisturizing and soothing effect along with significant improvement in healing
without scar formation. These positive benefits seen in this study might be due to the
synergistic action of the constituents of “Acne-N-Pimple Cream”.

Lenus culinaris is rich in polyphenols and the major monomeric flavans are catechin-3-
glucose, with lesser amounts of catechin and epicatechin.15 Alum (aluminium sulphate) acts
as potent stringent and antiseptic, which is beneficial in acne vulgaris.

The antioxidant properties of Aloe barbadensis have been well documented.16 Hu et al.
demonstrated the antioxidant activity of polysaccharide and flavonoid concentrations of Aloe


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barbadensis and found that the antioxidant activity was higher than that observed with alpha-
tocopherol.17 Caffeoyl aloesin is a powerful antioxidant compound isolated from Aloe
barbadensis, which has antiinflammatory and antioxidant activities. Aloesin has been shown
to inhibit tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of
tyrosinase from normal human melanocyte cell lysates.18 Bautista et al. demonstrated the anti-
inflammatory activity of Aloe barbadensis and documented the inhibition of bradykinin
activity.19

Vitex negundo has astringent, anti-inflammatory, analgesic (possibly mediated via
prostaglandin synthesis inhibition), antihistaminic, membrane stabilizing and antioxidant
activities.20 In one study, the flavonoid-rich fraction (5,7,3'-trihydroxy, 6,8,4'-trimethoxy
flavones) of Vitex negundo was found to antagonize the androgenic action of exogenous
testosterone propionate.21
Rani et al. documented the antibacterial and antifungal properties of Salmalia malabarica,
which are attributed to ‘shamimin’ a flavonol C-glycoside.22,23

Andrographis paniculata has immunomodulatory and antimicrobial effects, and the
antimicrobial activity is due to the synergistic effect of the arabinogalactan proteins and
andrographolides.24

Conclusion
Acne vulgaris is a common skin disorder, affecting virtually all adolescents and adults at
some time in their lives. Although the overall health is not impaired, acne is not a trivial
disease, as it can produce cutaneous and emotional scars that last a lifetime. The present study
was planned to evaluate the efficacy and safety of “Acne-N-Pimple Cream” in the
management of acne vulgaris.

This study observed significant reduction in number of blackheads and whiteheads, in number
of inflamed pustules and overall inflammation. Similarly, there was enhanced exfoliation,
moisturizing and soothing effect along with significant improvement in healing without scar
formation. There were no clinically significant short- and long-term adverse reactions, during
the entire period of the study and excellent patient compliance to “Acne-N-Pimple Cream”
was observed.

The excellent results obtained might be due to the antioxidant, anti-inflammatory,
antiandrogenic and antimicrobial properties of the ingredients of “Acne-N-Pimple Cream”
Therefore, it may be concluded that “Acne-N-Pimple Cream” is clinically effective and safe
in the management of acne vulgaris.

References
1.   Webster GF. Inflammation in acne vulgaris. J. Am. Acad. Derm. 1995; 33: 247-253.
2.   Kligman AM. An overview of acne. J. Invest. Derm. 1974; 62: 268-287.
3.   Koo J. The psychosocial impact of acne: Patient’s perceptions. J. Am. Acad. Dermatol.
     1995; 32: S26-S30.
4.   Cunliffe WJ. Acne and unemployment. Br. J. Derm. 1984; 115: 386.
5.   Cunliffe WJ, Gould DJ. Prevalence of facial acne in late adolescence and in adults. Br.
     J. Dermatol. 1979; 1: 1109-1110.
6.   Webster, Guy F. Acne vulgaris. Br. Med. J. 2002; 325(7362): 475-479.




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7.    Eady EA, Farmery MR, Ross JI, Cove JH, Cunliffe WJ. Effects of benzoyl peroxide and
      erythromycin alone and in combination against antibiotic-sensitive and -resistant skin
      bacteria from acne patients. Br. J. Dermatol. 1994; 131: 331-336.
8.    Eady EA. Bacterial resistance in acne. Dermatol. 1998; 196(1): 59-66.
9.    Leyden JJ, McGinley KJ, Cavalieri S, Webster GF, Mills OH, Kligman AM.
      Propionibacterium acnes resistance to antibiotics in acne patients. J. Am. Acad. Derm.
      1983; 8: 41-45.
10.   Reisner RM. Antibiotic and anti-inflammatory therapy of acne. Dermatol. Clin. 1983; 1:
      385-397.
11.   Burkhart CN, Gottwald L. Assessment of etiologic agents in acne pathogenesis.
      Skinmed. 2003; 2(4): 222-228.
12.   Briganti S, Picardo M. Antioxidant activity, lipid peroxidation and skin diseases. What’s
      new. J. Eur. Acad. Dermatol. Venereol. 2003;17(6): 663-669.
13.   del Marmol V, Teichmann A, Gertsen K. The role of combined oral contraceptives in
      the management of acne and seborrhea. Eur. J. Contracept Reprod. Health Care 2004;
      9(2): 107-124.
14.   Tan JK. Psychosocial impact of acne vulgaris: Evaluating the evidence. Skin Therapy
      Lett. 2004; 9(7): 1-3,9.
15.   Duenas M, Sun B, Hernandez T, Estrella I, Spranger MI. Proanthocyanidin composition
      in the seed coat of lentils (Lens culinaris L.). J. Agric. Food Chem. 2003; 51(27): 7999-
      8004.
16.   Saada HN, Ussama ZS, Mahdy AM. Effectiveness of Aloe vera on the antioxidant status
      of different tissues in irradiated rats. Pharmazie. 2003; 58(12): 929-931.
17.   Hu Y, Xu J, Hu Q. Evaluation of antioxidant potential of Aloe vera (Aloe barbadensis
      miller) extracts. J. Agric. Food Chem. 2003; 51(26): 7788-7791.
18.   Bautista-Perez R, Segura-Cobos D, Vazquez-Cruz B. In vitro antibradykinin activity of
      Aloe barbadensis gel. J. Ethnopharmacol. 2004; 93(1): 89-92.
19.   Yagi A, Takeo S. Anti-inflammatory constituents, aloesin and aloemannan in Aloe
      species and effects of tanshinon VI in Salvia miltiorrhiza on heart. Yakugaku Zasshi.
      2003; 123(7): 517-532.
20.   Dharmasiri MG, Jayakody JR, Galhena G, Liyanage SS, Ratnasooriya WD. Anti-
      inflammatory and analgesic activities of mature fresh leaves of Vitex negundo. J.
      Ethnopharmacol. 2003; 87(2-3): 199-206.
21.   Bhargava SK. Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo
      seeds: A histological and biochemical study in dogs. J. Ethnopharmacol. 1989; 27(3):
      327-339.
22.   Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for their anti-
      enteric potential against multi-drug resistant Salmonella typhi. Phytother. Res. 2004;
      18(8): 670-673.
23.   Faizi S, Ali M. Shamimin: A new flavonol C-glycoside from leaves of Bombax ceiba.
      Planta Med. 1999; 65(4): 383-385.
24.   Singha PK, Roy S, Dey S. Antimicrobial activity of Andrographis paniculata.
      Fitoterapia 2003; 74(7-8): 692-694.

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