clinical efficacy and safety of ampucare in …

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).


287


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


288


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


289


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


290


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


291


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.


292


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


293


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


294


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.


295




Figure 4: Images of selected cases pre & post healing with Ampucare

REFERENCES

1. Agrawal K, Chauhan N. Pressure ulcers: Back to the basics. Indian J Plast Surg, 2012;

45(2): 244–254.

2. Akbik D, Ghadiri M, Chrzanowski W, Rohanizadeh R. Curcumin as a wound healing

agent. Life Sci., 2014; 116; 1-7.

3. Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification

system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes

Care, 1998; 21: 855-9.

4. Attinger CE, Janis JE, Steinberg J, et al: Clinical approach to wounds: debridement and

wound bed preparation including the use of dressings and wound-healing adjuvants. Plast

Reconstr Surg, 2006; 117(7): 72S–109S.

5. Broughton G 2nd, Janis JE, Attinger CE: Wound healing: an overview. Plast Reconstr

Surg, 2006; 117(7): 1e-S–32e-S.

6. Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and

medicinal properties of neem (Azadirachta indica) Curr Sci., 2002; 82: 1336-5.


296


7. Biswas TK, Mukherjee B. Plant medicines of Indian origin for wound healing activity: a

review. Int J Low Extrem Wounds, 2003; 2: 25-39.

8. Bandyopadhyay et al. Clinical studies on the effect of Neem (Azadirachta indica) bark

extract on gastric secretion and gastroduodenal ulcer. Life Sci., 2004; 75: 2867-2878.

9. Chopra K, Kuhad A. Fight diabetes with physical activity and right dight. The tribune

January 30, 2008, Chandigadh, India.

10. Chauhan VS, Goel S, Kumar P, Srivastava S, Shukla VK. The prevalence of pressure

ulcers in hospitalized patients in a university hospital in India. J Wound Care, 2005; 14:

36–7.

11. Chaudhary M, Dwivedi VK, Naithani V. Clinical trial survey report of Ampucare done on

patients with different wounds. J Ecophysiol Occup Hlth, 2008; 8: 89-97.

12. Clark RAF. Cutaneous wound repairs. In: Goldsmith LA(ed.) Physiology, Bio- chemistry

and Molecular Bi-ology of skin. Oxford University Press, New York, 1991.

13. Chao CYL, Cheing GLY. Microvascular dysfunction in diabetic foot disease and

ulceration. Diab Metabol Res Rev, 2009; 25: 604-614.

14. Chambliss LR. Alternative and Complementary Medicine: An Overview. Clin Obstet

Gynaecol, 2001; 44: 640–52.

15. De D, Saxena S, Mehta G, Yadav R, Dutta R. Risk factor analysis and microbial etiology

of surgical site infections following lower segment caesarean section. Int J Antibiot, 2013;

283025.

16. Dixit Y, Kar A. Antioxidative activity of some vegetable peels determined in vitro by

inducing liver lipid peroxidation. Food Res Int., 2009; 42: 1351–4.

17. Dwivedi VK, Chaudhary M, Soni A, Naithani V, Shrivastava SM. Therapeutic role of

ampucare in alterations of antioxidant enzymes activities and wound healing effect in

Mus musculus Mice. J Ecophysiol Occup Hlth, 2008; 8: 167-176.

18. Dwivedi VK, Chaudhary M, Ahmad A, Soni A, Naithani V. Comparative efficacy of

Ampucare and silversulfadiazine against burn wound rat. J Appl Sci Res., 2010; 6(6):

674-682.

19. Eron LJ. Targeting lurking pathogens in acute traumatic and chronic wounds. J Emerg

Med., 1999; 17: 189–195.

20. Fabry et al. Fungistatic and fungicidal activity of east African medicinal plants. Mycoses,

1996; 39: 67-70.

21. Fulzule SV, Satturwar D, Joshi SB. Studies on anti-inflammatory activity of a polyherbal

formulation- Jatydi Ghrita. Indian Drugs, 2001; 39: 42–4.


297


22. Geethalakshmi R, Sakravarthi C, Kritika T, Kirubakaran M A, Sarada DVL, Evaluation of

antioxidant and wound healing potentials of Sphaeranthus amaranthoides Burm.f.

BioMed Res Int., 2013; 607109.

23. Hariti M, Rathee PS. Antifungal activity of the unsaponifiable fraction of the fixed oil of

Trichosanthes seeds. Asian J Chem., 1996; 8: 180–2.

24. Hollander JE, Singer AJ. State of the art laceration management. Ann Emerg Med., 1999;

34: 356–67.

25. Holzer SE, Camerota A, Martens L, Cuerdon T, Crystal-Peters J, Zagari M. Costs and

duration of care for lower extremity ulcers in patients with diabetes. Clin Ther., 1998; 20:

169-81.

26. Hariti M, Rathee PS. Antibacterial activity of the unsaponifiable fraction of the fixed oil

of Trichosanthes seeds. Asian J Chem., 1995; 7: 909–11.

27. Houghton PJ, Hylands PJ, Mensah AY, Hensel A, Deters AM. In vitro tests and

ethnopharmacological investigations: Wound healing as an example. J Ethnopharmacol,

2005; 100: 100-107.

28. Jaiswal S, Singh SV, Singh B, Singh HV. Plants Used for tissue healing of animals.

Natural Prod Rad., 2004; 3(4): 284‐290.

29. Kim et al. Antibacterial activity of Curcuma longa L. against methicillin-resistant

Staphylococcus aureus. Phytother Res., 2005; 19: 599-604.

30. Kurahashi T, Fujii J. Roles of Antioxidative Enzymes in Wound Healing. J Dev. Biol.,

2015; 3: 57-70.

31. Kuwahara M, Tada H, Mashiba K, Yurugi S, Iioka H, Niitsuma K, et al. Mortality and

recurrence rate after pressure ulcer operation for elderly long-term bedridden patients.

Ann Plast Surg, 2005; 54: 629–32.

32. Kumar B, Vijayakumar M, Govindarajan R, Pushpangadan P. Ethnopharmacological

approaches to wound healing exploring medicinal plants of India. J Ethnopharmacol,

2007; 114(2): 103-113.

33. Kundu et al. Turmeric (Curcuma longa) rhizome paste and honey show similar wound

healing potential: a preclinical study in rabbits. Int J Low Extrem Wounds, 2005; 4:

205-213.

34. Larijani B, Forouzandeh F. Diabetic foot disorders. Iran J Diab Lipid Disord, 2003; 2:

103-93.

35. Lilani SP, Jangale N, Chowdhary A, Daver GB, “Surgical site infection in clean and

clean-contaminated cases,” Indian J Med Microbiol, 2005; 23: 249–252.


298


36. Leng LL, Matthew NJM. Wound healing. The Singapore Family Phy, 2014; 40: 6-16.

37. Medeiros AC, Tertuliano AN, Azevedo GD, Vilar JP, Pinheiro LA, Neto JB: Surgical site

infection in a university hospital in north east Brazil. Brazilian J Infect Dis., 2005; 9(3):

310-4.

38. Martin A. The use of antioxidants in healing. Dermatol Surg, 1996; 22(2): 156-160.

39. Nourjah P. National Hospital Ambulatory Medical Care Survey: 1997 Emergency

Department Summary. Advance data from Vital and Health Statistics; no. 304.

Hyattsville, MD: National Center for Health Statistics, 1999.

40. National Burn Repository 2010 Report dataset version 6.0

http://www.ameriburn.org/2010NBRAnnualReport.pdf. Last accessed September 2, 2010

41. Phillips TJ, Machado F, Trout R, Porter J, Olin V. Falanga prognostic indicators in venous

ulcers. J Am Acad Dermatol, 2000; 43: 627-630.

42. Prakash et al. Total phenol, antioxidant and free radical scavenging activities of some

medicinal plants. Int J Food Sci Nutr, 2007; 58: 18-28.

43. Panchatcharam M, Miriyala S, Gayathri VS, Suguna L. Mol Cell Biochem, 2006; 290:

87-6.

44. Rhoads DD, Cox SB, Rees EJ, Sun Y, Wolcott RD. Clinical identification of bacteria in

human chronic wound infections: culturing vs. 16S ribosomal DNA sequencing. BMC

Infect Dis., 2012; 12: 321.

45. Surveillance of surgical site infection in England hospitals 1997–2001. National

Nosocomial Infection Surveillance Service. PHLS publication, 2001.

46. Somashekar S, Saraswati U, Laxinarayana U, Nagabushan S. Wound Healing Activity of

Ocimum sanctum. Linn with Supportive Role of Antioxidant Enzymes. Ind. J. Physiol

Pharmacol, 2006; 50(2): 163‐168.

47. Sunil SJ, Nitin Agrawal, Patil MB, Chimkode R, Tripathi A. Antimicrobial and wound

healing activities of leaves of Alternanthere sessilis. Linn. Int J Greenpharmacy, 2008;

141‐144.

48. Soni A, Dwivedi VK, Chaudhary M, malik K, Naithani V, Shrivastava SM. Plasma

cytokines and trace elements level in severe burn rat model with special reference to

wound healing potential of Ampucare. Res J Immunol, 2010; 3: 22-30.

49. Soni A, Dwivedi VK, Chaudhary M, Shrivastava SM, Naithani V. Efficacy of Ampucare:

a novel herbal formulation for burn wound healing versus other burn medicines. Asian J

Biol Sci., 2010; 3: 18-27.

50. Sen CK, Roy S. Redox signals in wound healing. Biochim Biophys Acta, 2008; 1780(11):


299


1348-1361.

51. Suntar I, Akkol EK, Nahar L, Sarker SD. Wound healing and antioxidant properties: do

they coexist in plants? Free Radicals Antioxidants, 2012; 2(2): 1-7.

52. Sidhu et al., Enhancement of wound healing by curcumin in animals. Wound Repair

Regen, 1998; 6: 167-177.

53. Sidhu et al. Curcumin enhances wound healing in Streptozotocin induced diabetic rats

and genetically diabetic mice. Wound Repair Regen, 1999; 7: 362-374.

54. Shivhare Y, Singour P, Patil UK, Pawar RS. Wound healing potential of methanolic

extract of Trichosanthes dioica Roxb. (fruits) in rats. J Ethnopharmacol, 2010; 127:

614–9.

55. Shrivastava SM, Kumar S, Chaudhary M. Time kill curve studies of Ampucare against E.

coli, S. aureus, K. Pneumoniae, P. vulgaris. Res J Med Plant, 2009; 3: 116-122.

56. Subapriya et al. Medicinal properties of neem leaves: a review. Curr Med Chem

Anticancer Agents, 2005; 5: 149-156.

57. Thomas DR, Diebold MR, Eggemeyer LM. A controlled, randomized, comparative study

of a radiant heat bandage on the healing of stage 3-4 pressure ulcers: a pilot study. J Am

Med Dir Assoc, 2005; 6(1): 46-49.

58. Tejada S, Manayi A, Daglia M, Nabavi SF, Sureda A, Hajheydari Z, Gortzi O, Pazoki-

Toroudi H, Nabavi SM. Wound healing effects of curcumin: a short review. Curr Pharm

Biotechnol, 2016; 17(11): 1002-7.

59. Yatomi Y, Igarashi Y, Yang L et al. Sphingosine 1-phosphate, a bioactive sphingolipid

abundantly stored in platelets, is a normal constituent of human plasma and serum. J

Biochem, 1997; 121: 969-973.

60. Zhang y, Steve A. McClain,3 Hsi-Ming Lee,1 Muna S. Elburki,1 Huiwen Yu,1 Ying Gu,4

Yu Zhang, 5 Mark Wolff, 2 Francis Johnson,5 and Lorne M. Golub. A Novel Chemically

Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced

Type I Diabetes: Initial Studies. J Diab Res., 2016; 2016.

clinical efficacy and safety of ampucare in …

Documents