Osman O.F.¹, Mansour I.S.², El-Hakim S.³

¹ Plastic and Reconstructive Surgery Unit, Al-Azhar University, Cairo, Egypt
² Microbiology Department, Al-Azhar University
³ Pathology Department, Al-Azhar University

SUMMARY. In this study a new invention (Honey Compound), made of honey plus some natural additives, was investigated for its use as a topical wound agent. Honey Compound obviates problems with the topical use of honey for wounds and burns. Laboratory investigation and animal laboratory studies have demonstrated superior results with honey compound in its antibacterial, antifungal, and wound-healing promotion properties compared with pure bee honey and some other topical wound agents.

Introduction

Throughout history, honey has been used because of its valuable medical properties. It has been found useful in the treatment of burns and wounds owing to its promotion of rapid healing through a number of mechanisms.1-3 Honey’s high osmolarity, acidic pH, inhibin factor, and nutrient content contribute to the inhibition of bacterial growth and the promotion of wound healing.

In spite of the high quality of pure bee honey as a topical wound agent, compared with other topical wound agents, its use is not without certain problems that may limit its optimal application, such as the intense local pain that the patient feels soon after its application. This may be intolerable, particularly in children, as also the excessive body fluid loss through the wound due to honey’s high osmolarity. This fluid loss has to be seriously considered because of its haemodynamic impact, especially in patients with major burns and in children.

Excessive fluid loss through the burn wound may alter the beneficial properties of the honey applied, by causing its rapid dilution and accelerating its washout from the wound surface.

It is also well known that within a few hours of application of honey dressing to the wound surface, the dressing will dry off because of evaporative water loss enhanced by body temperature, making subsequent dressing changes difficult and possibly compromising the natural wound healing process.

Honey Compound* presents an ideal solution to the problems presented by the use of pure bee honey** in wound management. Honey compound’s oily content acts as a barrier, preventing excessive loss of body fluid and decreasing evaporative wound water loss. It thus prevents wound desiccation and provides an optimal moist ambience for wound healing. The barrier effect also decreases local pain during and after wound manipulation.

The oily content of Honey Compound prevents the dressing from adhering to the wound surface. This facilitates subsequent dressing, without interrupting the wound healing process.

Honey Compound, with its natural additives, is designed for long-term coverage and provides the wound with nutritive and protective contents, thus improving wound antisepsis and nutrition and promoting healing in an optimal moist ambience.

In this study, we investigated and compared the in vitro antimicrobial activity both of Honey Compound and pure bee honey, and we designed an animal wound model to assess their effect on the promotion of wound healing.

Materials and methods

• The in vitro antimicrobial study was performed in the Microbiology Department of Al-Azhar University in two stages, employing standard microbial strains through the cup plate method according to Collee et al.16
  1. First stage. Five strains of bacterial -plus Candida were tested as to their zones of growth inhibition in mm against full concentration, 50%, and 25% dilutions of pure monofloral honey and Honey Compound made of the same honey.
  2. Second stage. The same bacterial strains plus Candida were tested against pure honey, Honey Compound, and three other known topical antibacterial agents, namely silver sulphadiazine cream 1%, gentamicin sulphate ointment 0.1%, and nitrofurazone ointment 0.2%. Zones of bacterial and fungal growth inhibition were measured in mm.
• The experimental study was performed in the animal laboratory at Al-Azhar University on 30 adult albino rats weighing 200-250 g. The animals were divided into three equal groups. Under general anaesthesia using ether inhalation, the animals’ dorsal skin was cleaned with ethanol and shaved. An excision measuring 6 ¥ 10 mm was made of an area of full-thickness skin on each side of the dorsum of each animal.

Wound treatment

The animals were kept in isolation cabinets.

Group 1. The animals were dressed twice daily with pure monofloral bee honey in the right-side (Rt) dorsal wounds and with silver sulphadiazine cream in the left-side (Lt) dorsal wounds.

Group 2. The animals were dressed twice daily with Honey Compound in the Rt dorsal wounds and with silver sulphadiazine in the Lt dorsal wounds.

Group 3. The animals were dressed twice daily with pure honey in the Rt dorsal wounds and Honey with Compound in the Lt dorsal wounds.

Wound measurements to assess the decrease in size were made every third day until complete wound healing, using standard wire mesh and counting the number of squares representing the exact wound size through close-up wound photographs.

Wound biopsies were performed on day 5 post-wound in all the wounds in order to assess cellular and fibrous healing activity at the edges and base of the wound. Biopsies were preserved in formalin 15% and prepared for haematoxylin and eosin staining.

Results

• In vitro bacteriological study
  • Both honey and Honey Compound effectively induced inhibition of bacterial growth, even at 50% and 25% dilutions (except with Pseudomonas strains) (Table I).
  • Our pure honey sample was not effective on Candida, while Honey Compound made of the same honey effectively induced reasonable bacterial growth inhibition even at 50% dilution (Table I).
  • Honey Compound induced larger inhibitory zones in all the bacteria tested and in Candida than pure honey at full concentration and in 50% and 25% dilutions (Table I).
  • Regarding the tested organisms’ zones of growth inhibition, honey and particularly Honey Compound were found to compare favourably with nitrofurazone ointment, silver sulphadiazine cream, and gentamicin ointment (Table II).
  • Honey Compound was found to effectively induce zones of inhibition in all the gram-positive and gram-negative bacteria tested and in Candida (Table II).
• Experimental study

  Wound healing period

  • In honey-treated wounds in group 1, the wound healing period lasted 9 ± 2 days.
  • In Honey-Compound-treated wounds in group 2, it also lasted 9 ± 2 days.
  • In group 3, the healing period was almost equal in the two wounds, with an average period of 8 ± 3 days.
  • In silver-sulphadiazine-treated wounds, in groups 1 and 2 the healing period was almost equal in the two groups, with an average of 12 ± 2 days.
  • Wound measurements showed a more rapid reduction in size in honey- and Honey-Compound-treated wounds than in silver-sulphadiazine-treated wounds and, contrastingly, almost equal changes in wound size in both honey- and Honey-Compound-dressed wounds (Table III).
  • Honey- and Honey-Compound-treated wounds were clean, tidy, and healthily granulating all the time, while silver-sulphadiazine-treated wound were almost covered by a purulent exudate with an untidy granulating surface.
  • Histological examination of wound biopsies showed increased thickening of the surface epithelium with an increase also in fibroblastic reaction and more deposition of collagen fibres in honey- and Honey-Compound-treated wounds than in silver-sulphadiazine-treated wounds (Figs. 1a, b, c).
  • Cellular and fibrous changes were almost similar in honey- and Honey-Compound-treated wounds, denoting an earlier, sound, and smooth healing process in comparison with silver-sulphadiazine-treated wounds.

Figs. 1A, B, C - Haematoxylin, eucine X 60.

Discussion

Honey was used in the treatment of wounds and burns by the ancient Egyptians and other civilizations thousands of years ago. Its use has continued in folk medicine until recent years.17 Many reports have recently been published demonstrating specific and detailed functions of its effective components as regards its antimicrobial and wound-healing promotion effects.

Problems of intense local wound pain and excessive loss of body fluids accompanying the use of pure honey, particularly in burn patients, make its use - in spite of the excellent results - a tough experience for both patient and surgeon.

Honey Compound with its natural additives, and particularly its oily content, prevents wound desiccation and the loss of body fluids and dressing adherence. It thus maintains an optimal, long-lasting, moist ambience for wound healing.

It was clear throughout this study that the in vitro antibacterial and antifungal efficacy of Honey Compound was not less but sometimes greater than that of pure honey, and its antifungal efficacy was far better than that of pure honey.

The wound-healing promoting capacity of honey and Honey Compound throughout our experimental animal study was almost equal, and compared favourably with silver sulphadiazine cream.

The histological examination of animal wound biopsies clearly demonstrates the enhancement effect of both honey and Honey Compound on both the cellular and the fibrous components of the wound-healing mechanism compared with silver sulphadiazine.

The natural additives in Honey Compound, together with its antibacterial and antifungal effects, open up new horizons, comparing favourably with honey and any of the known topical wound agents. If we consider its wound-healing promotion effects, Honey Compound is a real breakthrough as a topical agent for wounds and burns.

The beneficial effects of honey as a topical wound agent are beyond any doubt.1,3,5,12,17 The natural additives in Honey Compound obviate many of the problems encountered in the use of pure bee honey and they do not affect either its standard antibacterial and antifungal properties or its wound-healing promotion effects.

Conclusion

This study confirms the traditional positive effects of honey as a sound topical wound agent and demonstrates that Honey Compound has equal and even better results as regards its antimicrobial and antifungal properties and its wound-healing promotion effects.

RESUME. Dans cette étude les Auteurs ont investigué une nouvelle invention appelée Honey Compound (Composé de miel), faite de miel avec l’addition de certaines substances naturelles, pour ce qui concerne son emploi comme agent topique pour les lésions. Le Composé de miel évite les problèmes qui se vérifient avec l’emploi topique du miel dans les lésions et les brûlures. L’investigation en laboratoire et les études avec les animaux ont démontré les résultats supérieurs avec le Composé de miel pour ce qui concerne ses qualités antibactériennes, antifongiques et promotrices de la guérison par rapport au miel pur d’abeilles et d’autres agents topiques utilisés dans les soins des lésions.

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