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www.wjpr.net Vol 6, Issue 17, 2017.
286
Krishna et al. World Journal of Pharmaceutical Research
CLINICAL EFFICACY AND SAFETY OF AMPUCARE IN
TREATMENT OF DIFFERENT KINDS OF WOUNDS
Rama Krishna Gupta* and Hemlata Gupta
Sanvi Plastic, Burn and Cosmetic Surgery Clinic, Kampu, Lashkar, Gwalior (MP).
ABSTRACT
The study was aimed to analyze the effect of an Ayush approved poly
herbal formulation, Ampucare in the management of acute and chronic
non healing wounds. In the study, data of 1328 moderate to severe
wound patients suffering from bedsore (pressure ulcer), traumatic
wounds, diabetic wound, gangrene, burn patients, including low
immunity cancer patients treated between April 2013 to March 2017
were evaluated. Male: female ratio was 2.3:1 and out of 1328 patients,
the most common wounds among male were traumatic wounds which
accounted for 32.07% of cases (n=298) followed by bedsore (pressure
ulcer) wounds 27.5% (n=256), diabetic wounds 22.4% (n=208), burn
patients 10 % (n=93), gangrene 4.2% (n=39), and cancer patients wounds 3.7% (n=35).
Similarly for female patients, the most common wounds were traumatic wounds which
accounted for 26.8% of cases (n=107) followed by diabetic wound 22.5% (n=90), bedsore
(pressure ulcer), 17.04% (n=68), burn patients 16.3% (n=65), gangrene 9.02% (n=36) and
cancer patient wounds 8.3% (n=33). Our results revealed in terms of % reduction in size of
wounds after Ampucare treatment, the highest recovery was seen with wound of burn patients
(95.1%) followed by bedsore (93.8%), gangrene (92.8%), cancer patient wound (91.4%),
diabetic wound (88.4%) and traumatic wound (86.1). In conclusion, this retrospective study
strongly suggest the use of Ampucare for the treatment of various kinds wounds. It is safe,
well tolerated, effective to cure wounds in lesser time as it is having antiseptic, antioxidant
and anti‐inflammatory properties.
KEYWORDS: Ampucare, antioxidant, efficacy, retrospective, safety, wounds.
World Journal of Pharmaceutical Research SJIF Impact Factor 7.523
Volume 6, Issue 17, 286-299. Research Article ISSN 2277– 7105
Article Received on
25 October 2017,
Revised on 15 Nov. 2017,
Accepted on 05 Dec. 2017
DOI: 10.20959/wjpr201717-10307
*Corresponding Author
Rama Krishna Gupta
Sanvi Plastic, Burn and
Cosmetic Surgery Clinic,
Kampu, Lashkar, Gwalior
(MP).
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Krishna et al. World Journal of Pharmaceutical Research
INTRODUCTION
Chronic wound can be defined as a wound that does not heal in a predictable amount of time
as per normal stages of wound healing and is termed as a non-healing wound when it does
not improve after four weeks or does not heal in eight weeks. There are six main categories of
wounds: surgical, trauma, diabetic, venous, arterial, and pressure (Leng and Matthew, 2014).
Surgical wound which is a cut or incision occuring during surgery is generally acute. NNIS
service survey (1997–2001) has reported Staphylococcus aureus (47%) including MRSA and
Staphylococcus epidermidis (CONS) as the most common organism causing SSI (National
Nosocomial Infection Surveillance Service. PHLS publication, 2001). Lilani et al (2005) have
reported similar findings of predominance of Staphylococcus aureus in wound infections (De
et al., 2013) in their study observed predominance of Acinetobacter species (32.03%)
followed by S. aureus and coagulase negative Staphylococcus (21.09%).
A trauma wound is a severe break or injury in the soft tissue of the skin resulting from
accidents or acts of violence and can be worsen and become infected quickly if not treated
appropriately. It is the third most commonly encountered problems in the emergency
department (ED), accounting for 8% of the 95 million annual ED visits in the United States
(Nourjah 1999). S. aureus is considered to be the most problematic pathogen associated with
infected traumatic wounds (Eron 1999). Burns are also a type of traumatic injury caused by
thermal, electrical, chemical, or electromagnetic energy. Data from the 2010 ABA National
Burn Repository Report state that 71% of burn patients had burn sizes of less than 10% total
body surface area (TBSA). Diabetic wound can be defined as any break in the cutaneous
barrier, usually extending through the full thickness of the dermis (Larijani and Forouzandeh,
2003). As per the report of World Health Organization (October, 2013), 347 million people
have diabetes worldwide and it would be the 7th cause of mortality by 2030. According to a
report of Indian Council of Medical Research, there are approximately 35 millions diabetics
in Indian and this would increase to 80 million by 2030 (Chopra and Kuhad, 2008). Diabetic
foot ulcers can be of neuropathic, neuroischemic, and ischemic (Chao and Cheing, 2009).
Diabetic neuropathy is responsible for 50-75% of non-traumatic amputations (Holzer et al.,
1998). Neuropathy is present in more than 80% of patients with foot ulcers and increases the
risk of amputation 1.7 fold; 12 fold, if there is deformity, and 36 fold, if there is a history of
previous ulceration (Armstrong et al., 1998). Pressure-induced injuries impose a significant
burden not only on the patient but on the entire health care system. Patients with pressure
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Krishna et al. World Journal of Pharmaceutical Research
ulcers have high mortality rates (Agarwal and Chauhan, 2012). In spinal cord injury patients,
pressure ulcer occurs in 30-85% of patients during the first month of injury (Agarwal and
Chauhan, 2012). Kuwahara et al. (2005) reported 68.8% mortality amongst elderly patients
because of pressure ulcer. In Indian setting, the prevalence of pressure ulcers in hospitalized
patients has been reported to be 4.94% in a study conducted by (Chauhan et al., 2005).
Wound infections are the cumulative result of several factors such as, the inoculum of
bacteria introduced into the wound during the procedure, the virulence of the contaminants,
the micro-environment of each wound and the integrity of the patient-host defence
mechanisms and represents a substantial burden of disease for patients and health services.
(Medeiros et al. 2005). The ultimate goals of wound management are to avoid infection and
achieve a functional and cosmetically acceptable scar (Hollander and Singer 1999).
The complete wound healing is a complex process associated with various mechanisms of
tissue repairs, including inflammation, granulation tissue formation, reepithelization,
angiogenesis and contraction (Yatomi et al., 1997). The contribution of each process varies
according to the type of wound (Grinnel, 1994). Wounds become chronic or non healing
when healing is impaired at any stage due to necrosis caused by factors external to the cell or
tissue, such as infection, toxins, or trauma which result in the unregulated digestion of cell
components. Therefore, various mechanisms are required to be taken care of in parallel for a
complete wound healing.
Antioxidants have been shown to play an important role in the progression of wound healing
(Suntar et al., 2012; Martin 1996). Besides, anti-inflammatory agents act as a key role in the
wound healing process and preventing exacerbating wound conditions (Sen and Roy, 2008).
Antimicrobial agents are also useful in the management of microbial infection which may
concomitantly occur in severe and chronic wounds (Rhoads et al., 2012). There are plenty of
different herbs that have been proven to possess anti‐inflammatory and anti‐microbial
properties that could also enhance the wound healing (Jaiswal et al., 2004; Geeta lakshmi et
al., 2013; Kurahashi and Fujii, 2015).
Because of the toxicity and side effects of chemical agents (allopathic drugs), the importance
and efficacy of traditional and complementary medicine have risen in recent years.
Approximately, four billion people across the world have been using plants as medicines
because of their fewer side effects and are more cost-effective in comparison with chemical
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Krishna et al. World Journal of Pharmaceutical Research
agents (Chambliss, 2001;Rhoads et al., 2012;Kumar et al., 2007).
Efforts are being made worldwide to discover newer drugs that can promote wound healing
with minimal side effects and to reduce the cost of hospitalization and management of
complications. It is believed that herbal formulations with multiple plants could have greater
effects than the same herbs used individually. These synergistic effects enhance the desired
action with reducing the cost of hospitalization. Ampucare, supplemented with goodness of
bark of Azadirachta indica, rhizome of Curcuma longa and leaves of Trichosanthes dioica
along with other herbs in base oil for topical application, approved by regulatory bodies in
India, has been evaluated retrospectively for the management of different kinds of wounds.
The aim of this retrospective study was to evaluate the efficacy and safety of Ampucare in the
treatment of various kinds of wounds with moderate to severe in Indian patients including
low immunity cancer patient wounds.
MATERIALS AND METHODS
Study Design
This retrospective study was done by collecting data from multiple hospitals including BIMR
Hospital Gwalior, KDJ memorial Hospital, Gwalior, Navjivan Hospital, Gwalior, Asian
Hospital, Gwalior, SIMS Hospital, Gwalior, India. The data of 1328 patients suffering from
moderate to severe types of wounds which Included majorly traumatic wounds followed by
bedsore (pressure ulcer), diabetic wound, burn patients, gangrene and cancer patients wounds
treated between April 2013 to March 2017 were evaluated during the analysis. Further, the
P a t i e n t s w h o h a d the history of hypersensitivity to any of the ingredients/
herbs were not included in the study. All procedures followed were in accordance with the
ethical standards of the responsible committee on human experimentation (institutional and
national) and with the Helsinki Declarartion of 1975, as revised in 2000 and 2008. Informed
consents were not obtained as study being retrospective study. No co-morbidity was recorded
into the case record form. No other topical product was applied except Ampucare.
Drugs
An oily Lotion Ampucare was used. The ingredients of Ampucare synergistically act on the
wound from the initial stage of wound healing till re-epithelization and wound closure. All
these ingredients possess strong antimicrobial activity and synergistically activate fibroblasts,
collagen synthesis and promotes effective granulation leading to re-epithelialization (Biswas
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Krishna et al. World Journal of Pharmaceutical Research
and Mukherjee, 2003; Kundu et al., 2005; Sidhu et al., 1998; Sidhu et al., 1999).
The details of active ingredients of this formulation are as follows:
Curcuma longa
Curcuma longa present in Ampucare acts as a checkpoint to prevent undesirable
inflammation, free radical generation and pain that may hamper wound healing. It further
enhances transforming growth factor-beta (TGF-b), migration of cells such as myofibroblasts,
fibroblasts and macrophages which are essential for wound healing and reepitheliazation
(new skin formation) (Fabry et al., 1996; Subapriya et al., 2005).
Azadirachta indica
Azadirachta indica in synergism with curcumin extends anti-microbial activity to Ampucare
and helps prevent undue infection at the wound area (Bandyopadhyay et al., 2004; Fabry et
al., 1996; Subapriya et al., 2005).
Trichosanthes dioica
Trichosanthes dioica promotes cellular proliferation and collagen synthesis at the wound site
by increase in total protein, total collagen and hydroxyproline contents of granulation tissues.
Dosage schedule
Depending on the severity and size of the wounds, the dosage schedule for the Ampucare
application varied from patients to patients. However, majority of the patients received a dose
of 4 ml Ampucare/ cm3wound area (length of wound *breadth of wound *depth of wound).
For patients with moderate to severe wounds, Ampucare dressing was replaced once every
day initially till granulation started and then once in three days. The duration of the therapy
was 10 to 60 days.
End of the therapy evaluation
The efficacy of the topical wound healing lotion was evaluated at the end of the therapy by
calculating the % reduction compared to baseline.
RESULTS AND DISCUSSION
Typically, there are four phases of normal wound healing which includes haemostasis,
inflammation, proliferation and remodeling. Wound healing processes are well organized
biochemical and cellular events leading to the growth and regeneration of wounded tissue in a
special manner (Attinger et al. 2006; Broughton et al. 2006). Healing of wounds involves the
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Krishna et al. World Journal of Pharmaceutical Research
activity of an intricate net work of blood cells, cytokines and growth factors which ultimately
leads to the restoration to normal condition of the injured skin or tissue (Clark, 1991).
Antioxidants counter the excess proteases and reactive oxygen species (ROS) often formed
by neutrophil accumulation in the wounded area and protect protease inhibitors from
oxidative damage. Fibroblasts and other cells may be killed by excess ROS and skin lipids
will be made less flexible, so antioxidant substances will reduce the possibility of these
adverse events occurring. Because of these several factors, overall antioxidant effects appear
to be important in the successful treatment of wounds (Houghton et al, 2005; Panchatcharam
et al., 2006).
In the current retrospective analysis, a total of 1328 patients were evaluated of which 929
patients (69.95%) were male with median age 56.7± 9.7 years whereas 399 patients (30.04%)
were female with median age 57.0± 15.2 years (Table 1). Of 929 male patients, the most
common wounds were traumatic wounds which accounted for 32.07% of cases (n=298)
followed by bedsore (pressure ulcer) wounds 27.5% (n=256), diabetic wounds 22.4%
(n=208), burn patients 10 % (n=93), gangrene 4.2% (n=39), and cancer patients wounds 3.7%
(n=35). Of 399 female patients, the most common wounds were traumatic wounds which
accounted for 26.8% of cases (n=107) followed by diabetic wound 22.5% (n=90), bedsore
(pressure ulcer), 17.04% (n=68), burn patients 16.3% (n=65), gangrene 9.02% (n=36) and
cancer patient wounds 8.3% (n=33) (Table 2). Analysis of anatomical location of wounds
revealed that the affected part of the majority of the patients were on leg or foot accounted for
23.5 % (n=313) followed by arm 19.0% (n=253%), upper and lower back wound 17.6%
(n=234), ankle 12.4% (n=165), knee 8.6% (n=114), toe and sole 7.4% (n=98), others 6.5%
(n=86) and head 4.9% (n=65) (Table 3).
Wound size and duration of treatment are important variables of wound healing (Phillips et
al., 2000). Our results revealed that all the patients showed a good treatment response with
Ampucare. The duration of treatment of wound depends on types and size of wound. In burn
cases, resuscitation fluid were adminsitered as base therapy with fluid rates guided by urine
output, and vital signs monitoring. Systemic antibiotics were co-admiistred in case of severe
burn wounds for initial 7-10 days along with ampcare post that period only Ampucare was
applied. Burn patients wound showed 95.1% reduction in the wound size in just 38 days of
treatment.
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In bed sores, diabetes was present in 20% cases with hypertension in another 30% and
underlying kideny diases in 15% cases, and suitable therapies were coadministred. Wound of
bedsore (pressure ulcer) showed a 93.8% decreased in 60 days. Thomas et al., (2005) have
shown that pressure sores have poor healing rates and only 75% of stage two ulcers heal in
two months. After 59 days of treatment, the gangrene showed a 92.8% decrease in size of
wound. In c a n c e r p a t i e n t s no other infection and inflamamtion management
drug was given except for anticancer therapy. Approximately 91.4% reduction in cancer
patients wound size was noted in 51 days of Ampucare application. For d i a b e t i c ,
diabetes was present in 100% cases with no other comorbidity and cases were handled only
with d i a b e t e s management therapy along with topical Ampucare. After 47 days of
Ampucare treatment, diabetic wound reduced 88.4% which is in line with previous study
conducted by Dandekar (2015) who have noticed that nearly 95% patients were clinically
cured after treatment with Ampucare with 96.2 % healing in wound after treatment for 45
days.
In traumatic cases only single shot of prophylactic antibiotic was given and rest was managed
with Ampucare. Close to 86.1% reduction in size of traumatic wound in just 28 days of
treatment (Table 4). Overall, in terms of % reduction in size of wounds, the highest recovery
was seen with wound of burn patients followed by bedsore, gangrene, cancer patient wound,
diabetic wound and traumatic wound. Photographs of some patients (who gave their consent)
have been shown in Figure 1. The significant activity of Ampucare in different kinds of
wound healing is associated with synergistic activity of Azadirachta indica, rhizome of
Curcuma longa and leaves of Trichosanthes dioica. Earlier it has been reported that A. indica
has anti-inflammatory, antihyperglycaemic, antibacterial, antiviral, antioxidant,
antimutagenic, wound repair and anticarcinogenic properties (Biswas et al., 2002; Prakash et
al., 2007). Curcumin because of its antioxidant, radical scavenger, antimicrobial and anti-
inflammatory activities has been shown to act on different stages of the wound healing
process to enhance healing (Akbik et al., 2014; Tejada et al., 2016; Zhang et al., 2016). Fabry
et al., (1996) demonstrated that curcumin enhances the rate of wound healing by improving
rates of epithelialisation, wound contraction and tensile strength. Curcumin has been shown
to accelerate wound healing by decreasing the levels of lipid peroxides (LPs), while the
increasing the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(Gpx) (Fabry et al., 1996; Kim et al., 2005). Previous studies have demonstrated better
maturation and cross linking of collagen in the curcumin treated rats, by increasing stability
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Krishna et al. World Journal of Pharmaceutical Research
of acid-soluble collagen, aldehyde content, shrinkage temperature and tensile strength in
diabetic wound (Panchatcharam et al., 2006; Biswas and Mukherjee, 2003).
Azadirachta indica in synergism with curcumin extends antimicrobial activity to Ampucare
and helps prevent undue infection at the wound area (Bandyopadhyay et al., 2004; Subapriya
et al., 2005).
Trichosanthes dioica has also been reported to have antiinflammatory activity, antibacterial
activity, anti-fungal activity, antioxidant activity and wound healing activity (Dixit and Kar,
2009; Shivhare et al., 2010;Fulzule et al., 1999; Hariti and Rathee, 1996; Hariti and Rathee,
1995). Further, the wound healing potential of Trichosanthes dioica has been studied in rats
(Shivhare et al., 2010). Ampucare has been proven to act by multiple modes of action with
strong antibacterial activity against difficult to treat pathogens. A potent wound healing
efficacy has already been reported for this product (Dwivedi et al., 2008; Dwivedi et al.,
2010; Soni et al., 2010A; Soni et al., 2010B; Chaudhary et al., 2008). Many researchers have
demonstrated that wound healing can be improved by herbal drugs having antiseptic,
antioxidant and anti‐inflammatory properties (Somashekar et al., 2006; Sunil et al., 2008).
In conclusion, this retrospective study strongly suggest the application of Ampucare provides
o v e r a l l wound healing in patients with various kinds of wounds. Compared to other
drugs, it is economic, safe, well tolerated and effectively cure wounds in lesser time. So
Ampucare can be chosen for the treatment of various kinds of wounds.
Table 1: Baseline demographic characteristics of the patients.
Characteristic Ampucare treatment group
Total no. of patients 1328
No. of male patients 929 (69.95%)
No. of female patients 399 (30.04%)
Median age of male patients 56.7± 9.7 years
Median age of female patients 57.0± 15.2 years
Table 2: Types of wounds included into study.
Wounds covered into study Total Male Female
Traumatic wounds 405 298 107
Bedsore (pressure ulcer) 324 256 68
Diabetic wound 298 208 90
Burn patients 158 93 65
Gangrene 75 39 36
Cancer patients wounds 68 35 33
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Krishna et al. World Journal of Pharmaceutical Research
Total 1328 929 399
Table 3: Anatomical location of wounds.
Anatomical location Frequency (n)
Leg or foot 313
Knee 114
Toe and sole 98
Arm 253
Ankle 165
Head 65
Upper and lower back wound 234
Others 86
Table 4: Comparison of reduction in wound surface area.
Wounds
Wound area (cm2
) % Reduction
compared to
baseline
Average
treatment
days Start of the
Treatment
Mid of the
treatment
End of the
Treatment
Bedsore
(pressure ulcer) 16.3 ±1.9 9.3 ±1.0 1.0±0.1 93.8 60
Traumatic
wounds 29.5 ±1.4 19.2 ±0.8 4.1±0.1 86.1 28
Diabetic
wound 11.2 ±1.6 5.3 ±1.0 1.3±0.1 88.4 47
Burn patients 18.5 ±1.9 9.6 ±1.1 0.9±0.1 95.1 38
Cancer patients
wounds 8.2 ±2.1 4.1 ±0.9 0.7±0.1 91.4 51
Gangrene 9.8 ±1.4 5.2 ±1.1 0.7±0.1 92.8 59
Figure 1: Images of selected cases pre & post healing with Ampucare.
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Figure 2: Images of selected cases pre & post healing with Ampucare.
Figure 3: Images of selected cases pre & post healing with Ampucare.
Figure 4: Images of selected cases pre & post healing with Ampucare
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