Wound healing compositions comprising buckwheat honey and methylglyoxal and methods of use

Abstract

The invention provides compositions based on medicinal honey containing broad-spectrum antibacterial activities of peroxide, polyphenols and methylglyoxal, for the treatment of wounds; and methods of treating a wound, comprising contacting a wound with the above composition or a wound dressing containing the above composition.

Claims

1. A wound healing composition consisting essentially of: buckwheat honey; and methylglyoxal in an amount of from about 500 to about 2000 mg per kg of the total composition.

2. A wound healing dressing comprising: the wound healing composition according to claim 1; and a support.

3. The wound healing dressing of claim 2, wherein the support is selected from the group consisting of a fibrous gauze material, a hydrogel, a foam, a film, a hydrocolloid, a collagen, an alginate, and a combination of two or more thereof.

4. The wound healing dressing of claim 2, wherein the wound healing dressing is capable of being replaced on a wound at least once.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The nature and mode of operation of the present invention will now be more fully described in the following detailed description of the invention taken with the accompanying figures, in which:

(2) FIG. 1, panels 1A, 1B, 1C, and 1D, shows treatment using the composition of the present invention, MGO-fortified buckwheat honey wound dressings, of a large infected amputation wound in the foot of a diabetic patient.

(3) FIG. 2, panels 2A, 2B, 2C, and 2D, shows treatment using the composition of the present invention, MGO-fortified buckwheat honey wound dressings, of a large deep pressure ulcer.

DETAILED DESCRIPTION OF THE INVENTION

(4) While the present invention is described with respect to what is presently considered to be the preferred aspects, it is to be understood that the invention as claimed is not limited to the disclosed aspects.

(5) Furthermore, it is understood that this invention is not limited to the particular methodology, materials and modifications described and as such may, of course, vary. It is also understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to limit the scope of the present invention, which is limited only by the appended claims.

(6) Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention belongs. Although any methods, devices or materials similar or equivalent to those described herein can be used in the practice or testing of the invention, the preferred methods, devices, and materials are now described.

(7) The present invention provides an exemplary wound healing composition, which includes seasonally harvested raw, strained, monofloral buckwheat honey naturally rich in hydrogen peroxide (containing and/or capable of generating 2-4 mM concentration), polyphenols (275-575 gallic acid equivalents of polyphenol compounds per gram of honey) to which is added the natural antibacterial compound, methylglyoxal to a final concentration of 500-2000 mg per kg of final honey product. This MGO-fortified buckwheat honey has broad-spectrum peroxide and non-peroxide antimicrobial activity effective to reduce the number of viable microorganisms at a wound site.

(8) In another aspect, the present invention provides a wound dressing. The wound dressing is used with the composition and a support. The support includes, but is not limited to, a fibrous gauze material, a hydrogel, a foam, a film, a hydrocolloid, an alginate, a collagen, or a combination of any two or more of the afore-mentioned.

(9) In yet another embodiment, the present invention includes a method of treating a wound. The method includes contacting a wound with any of the above embodiments of the wound dressing.

(10) A chronic wound, non-healing wound, slow-to-heal wound, or stalled wound, as used herein, refers to a wound that fails to heal spontaneously over a 4-12 week timeframe from inception of the wound to complete closure of the skin at the wound site. Such wounds commonly include external dermal wounds.

(11) Skin wounds designated as chronic or non-healing or slow-to-heal or stalled are commonly observed in clinical settings as venous leg ulcers, diabetic foot ulcers, pressure ulcers, arterial ulcers, ulcers of mixed etiology, burns, or non-healing surgical wounds. Other types of non-healing wounds are observed in less frequent conditions, such as, fistulae, dermatitis or vasculitis wounds, skin cancers, and radiation burns. This list is not exhaustive and is provided to show examples of such non-healing wounds. Differentiated from acute wounds that spontaneously heal without complications in a matter of days or weeks through the four normal phases of the wound healing curve (hemostasis, inflammation, proliferation, and remodeling), chronic wounds may persist for months or years and occasionally can last a lifetime, and are therefore commonly referred to as non-healing wounds. There is a need for treatment of any of these types of non-healing wounds since spontaneous healing has failed to occur. In chronic wounds, at the cellular biological level, there is commonly a prolonged inflammatory phase often caused by elevated proteases or active infection.

(12) Sometimes prolonged inflammation due to elevated wound proteases and active infection occur simultaneously and prevent wounds of the skin from healing. The present disclosure relates to a composition, and methods for treating wounds of the skin to counteract these pathological conditions. The composition includes a medicinal honey fortified with the additional antimicrobial compound methylglyoxal. The components of the inventive composition surprisingly provide a synergistic effect that results in broad-spectrum peroxide and non-peroxide antibacterial activity that acts to provide suppression of wound protease activities and active infections.

(13) The composition according to the present invention is useful for treating common chronic wounds, such as venous leg ulcers, diabetic foot ulcers, pressure ulcers, arterial ulcers, burns, and non-healing surgical wounds. In addition, the composition according to the present invention is also useful for treating abrasions, lacerations, minor cuts, scalds and burns, and other partial thickness wounds. A useful composition includes, but is not limited to, medicinal honey and methylglyoxal. The composition is advantageously applied in an ointment that is applied to a wound until it is healed (3-8 months) with wound dressing changes every 24-96 hours. Alternatively, the wound healing composition of the present invention is impregnated into or associated with carrier dressing supports (e.g. fibrous gauze, hydrogel, foam, film, hydrocolloid, collagen, or alginate), which are applied to wounds for the times described above.

(14) The present disclosure further provides a method for treating the wound. In some embodiments, the method includes contacting a wound with the composition of the present disclosure wherein the composition includes a medicinal honey fortified with the natural non-peroxide antibacterial compound, methylglyoxal comprising an amount between 500-2000 mg per kg of finished wound healing composition, effective to reduce the number of viable microorganisms at a wound site. The composition is applied to the wound, for example, in an ointment. In some embodiments, the composition is applied to a wound dressing, which is subsequently applied to the wound. Advantageously, a dressing including the composition is contacted with the wound until it is healed (3-8 months) with wound dressing changes every 24-96 hours, thereby providing a moist environment enriched with the MGO-fortified medicinal honey to facilitate healing of the skin or mucosal membrane.

Embodiments

(15) Embodiment 1 is a composition including a medicinal honey with high peroxide-induced and polyphenol-facilitated antimicrobial activity, an effective amount of methylglyoxal (500-2000 mg per kg) to add non-peroxide antimicrobial activity, wherein each of the antimicrobial activities provides a different mechanism of antibacterial inhibition thereby providing a broad-spectrum antimicrobial activity effective to reduce the number of viable microorganisms at a wound site.

(16) Embodiment 2 is the composition of embodiment 1 wherein the medicinal honey is monofloral buckwheat honey that naturally generates 2-4 mM hydrogen peroxide and which naturally contains 275-575 gallic acid equivalents of polyphenol compounds per gram of honey, and wherein the amount of methylglyoxal added is 500-2000 mg per kg of honey.

(17) Embodiment 3 is a wound dressing including the composition of either embodiment 1 or 2; and a support.

(18) Embodiment 4 is a wound dressing of embodiment 3, wherein the support includes a fibrous gauze material, a hydrogel, a foam, a film, a hydrocolloid, an alginate, a collagen, or a combination of any two or more of the afore-mentioned.

(19) Embodiment 5 is a method of treating a wound, including contacting a wound with the composition of either embodiment 1 or 2.

(20) Embodiment 6 is a method of treating a wound, including treating a wound with the wound dressing of either one of embodiments 3 or 4.

Examples

(21) Objects and advantages of this invention are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit to this invention.

(22) Example 1 demonstrates the composition of the present invention, embodiments 1 and 2.

(23) Monofloral buckwheat honey fortified with methylglyoxal at a concentration of 1000 mg per kg is prepared and impregnated into acetate non-woven medical grade dressing (approximately 4 g MGO-fortified buckwheat honey in each 4-inch5-inch dressing), embodiments 3 and 4. The dressings are protected with polyethylene liners applied to both sides, and dressings of 4-inches5-inches are sealed individually in foil pouches constructed of white polyester film fused to aluminum foil that constitutes an excellent barrier. The dressings are then sterilized with gamma radiation and verified as sterile before use.

(24) Panels 1A, 1B, 1C, and 1D of FIG. 1, show treatment using dressings impregnated with the composition of the present invention, MGO-fortified buckwheat honey, of a large infected open amputation wound in the foot of a diabetic patient, embodiments 5 and 6. A 47 year-old male with a history of plantar diabetic foot ulcers who had recently had all the toes on his left foot amputated and the dermal layer on a significant portion of the underside of his foot excised to remove infected tissue (Panel 1A) presented with extensive infection in the open wound on the plantar aspect of his foot. After sharp debridement of this severely infected open amputation wound to remove slough, eschar, and necrotic tissue, the manufactured sterile MGO-fortified buckwheat honey dressings were cut to closely fit the wound size using sterile scissors and applied to the wound, with dressing changes every two days (48 hours). On day 0, the wound measured 12 cm8 cm (Panel 1A: wound area 96 cm.sup.2). The patient was instructed on how to change his own dressings every 48 hours. After three weeks of treatment with the sterile MGO-fortified buckwheat honey dressings, the wound area decreased 7.8-fold to 12.25 cm.sup.2 (Panel 1B), a wound area reduction of 87%. Many wound healing trajectory studies in the literature indicate that a wound area reduction of greater than 50% within 4 weeks of treatment indicates that full wound closure will occur within 12-20 weeks of continued treatment. This wound was no exception to that expectation, fully closing after 12 weeks of treatment with the MGO-fortified buckwheat honey dressings, having a wound area of 2.6 cm.sup.2 after 8 weeks of treatment (Panel 1C), and less than 0.4 cm.sup.2 after 11 weeks of treatment (Panel 1D).

(25) Example 2 demonstrates the composition of the present invention, embodiments 1 and 2.

(26) Panels 2A, 2B, 2C, and 2D, depicted in FIG. 2, show treatment using dressings impregnated with the composition of the present invention, MGO-fortified buckwheat honey, of a large deep pressure ulcer. The MGO-fortified buckwheat honey dressings were used to treat this pressure ulcer situated on the right heel of a 59 year-old male. This patient has a history of diabetes and immobility. Before onset of treatment with the sterile MGO-fortified buckwheat honey dressings, the wound measured approximately 6.3 cm4.4 cm (Panel 2A: 27.7 cm.sup.2). The patient was instructed on how to change his own dressings every 48 hours. After three weeks of treatment with the sterile MGO-fortified buckwheat honey dressings, the wound area had decreased to 11.2 cm.sup.2 (Panel 2B), a 60% reduction in the wound area, and again greater than the 50% wound area reduction within 4 weeks of treatment that is indicative of complete closure within a 12-20 week time frame. This large pressure ulcer had reduced in wound area to 4.4 cm.sup.2 after 9 weeks of treatment (Panel 2C), and as expected, went on to completely close after 13 weeks of treatment with the sterile MGO-fortified buckwheat honey wound dressings (panel 2D).

(27) Thus, it is seen that the objects of the present invention are efficiently obtained, although modifications and changes to the invention should be readily apparent to those having ordinary skill in the art, which modifications are intended to be within the spirit and scope of the invention as claimed. It also is understood that the foregoing description is illustrative of the present invention and should not be considered as limiting. Therefore, other embodiments of the present invention are possible without departing from the spirit and scope of the present invention.