WO2012134770A1

WO2012134770A1 - Honey composition

Info

Publication number: WO2012134770A1
Application number: PCT/US2012/028438
Authority: WO
Inventors: Anne Marie WIBAUX
Original assignee: Avery Dennison Corporation
Priority date: 2011-03-25
Filing date: 2012-03-09
Publication date: 2012-10-04

Abstract

Various adhesive and rubber compositions are described that comprise honey. The compositions can be incorporated into medical articles such as wound dressings or bandages. Also described are various methods of use involving the honey containing compositions.

Description

HONEY COMPOSITION

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims priority upon US provisional application serial No.

61/467,553 filed March 25, 2011.

FIELD OF THE INVENTION

[0002] The present invention relates to a composition containing a combination of polymeric components and honey. The composition can be used in a wide array of medical products and provides a convenient technique for incorporating honey therein.

BACKGROUND OF THE INVENTION

[0003] The beneficial properties of certain honeys, particularly Manuka honey, include anti-bacterial properties and a peroxide activity. These properties have been shown to inhibit the growth of various species of bacteria and limit the production of undesirable by-products of bacterial growth. Honey with at least 10% peroxide activity, i.e. 10% phenol equivalent, typically demonstrates these therapeutic values.

[0004] In view of these known properties of honey, various practices are known in which honey is applied to a wound. Methods of applying honey to a wound are varied and include soaking cotton gauze in honey or forming a honey-containing ointment or a "rubbery gel" as is known in the art. Commercial products containing honey are also available for treating wounds.

[0005] Honey impregnated dressings are known. However, a disadvantage of those dressings is that wound exudate dilutes and washes the honey away from the wound. In addition to cleaning exudate and honey from the wound, such dressings typically become messy and must be frequently replaced.

[0006] Also known is a commercially available honey which is pliable and formable.

However, when such composition is used in conjunction with a dressing and placed in contact with wound fluid, the dressing typically loses its integrity and as with previous products the honey tends to wash away.

[0007] While honey can be applied to a wound area, the typical fluidity of honey has made localized application difficult. Even the use of absorbent material, such as used in known bandages or gauzes, has not successfully addressed the difficulties relating to the application of honey to, and its maintenance on, the wound area. Wounds having exudating flows exacerbate this problem. Therefore, a need exists for an appropriate dressing in conjunction with honey in a form that overcomes the previously noted problems.

[0008] Furthermore, it would be advantageous to provide a honey based wound dressing that meets the requirements of moist wound care practice, is easy to apply, stays in place on the wound, does not disintegrate in the wound bed and particularly while in contact with the wound exudates.

[0009] Moreover, it would be beneficial to provide a honey based adhesive composition that addresses the previously noted disadvantages, and/or provides a useful and convenient technique of using honey in a wound healing method or in related articles.

[0010] Another difficulty associated with the use of honey in wound care is that the processing of honey at high temperature, i.e. higher than 50°C, leads to a loss of antimicrobial efficacy. It is typically necessary to subject honey to such temperatures when incorporating such into a wound treating composition or medical article. Accordingly, it would also be beneficial to provide a formulation which could be processed at low temperatures, thereby maintaining the antimicrobial and antiinflammatory properties of the honey.

SUMMARY OF THE INVENTION

[0011] The difficulties and drawbacks associated with previously known compositions, medical articles, and related methods are addressed in the present composition, apparatus and method for various honey based compositions and related aspects.

[0012] In one aspect, the present invention provides a composition comprising from about 5 parts to about 55 parts of an adhesive or rubber component and from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey.

[0013] In another aspect, the present invention provides a medical article comprising a composition including from about 5 parts to about 55 parts of an adhesive or rubber component and from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey. [0014] In yet another aspect, the invention provides a method of forming a composition containing honey. The method comprises providing from about 5 parts to about 55 parts of an adhesive or rubber component and providing from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey. The method also comprises blending the adhesive or rubber component with the matrix including honey.

[0015] In still another aspect, the invention provides a method for treating a wound comprising providing a medical article including from about 5 parts to about 55 parts of an adhesive or rubber component, and from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey. The method also comprises applying the medical article over the wound.

[0016] As will be realized, the invention is capable of other and different embodiments and its several details are capable of modifications in various respects, all without departing from the invention. Accordingly, the description is to be regarded as illustrative and not restrictive.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0017] Generally, the present invention provides a composition comprising from about

5 parts to about 55 parts of an adhesive or ru bber component preferably including one or more polyisobutene and/or styrene block type copolymers, and from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey. All references herein to parts are parts by weight. The composition may optionally comprise one or more aqueous natural or synthetic gelling agents. The composition may also optionally comprise one or more medicinal agents. The invention also provides various medical articles and devices containing the composition. And, the invention additionally provides various methods of use involving the composition. All of these aspects are described in greater detail as follows.

Adhesive or Rubber Component

[0018] As noted, the preferred embodiment compositions comprise an adhesive or rubber component. The adhesive or rubber component preferably includes one or more polyisobutene and/or styrene block type copolymers. Block copolymers have been produced which comprise primarily those having a general structure A— B and A— B— A wherein the polymer blocks A comprise thermoplastic polymer blocks such as polystyrene, while block B is an elastomeric polymer block such as polyisobutene. The proportion of the thermoplastic blocks to the elastomeric polymer block and the relative molecular weights of each of these blocks is balanced to obtain an adhesive or a rubber having unique performance characteristics. [0019] Generally, any adhesive or rubber phase containing one or more polyisobutenes and/or styrene radical block type copolymers can be used. A representative and suitable polyisobutene is commercially available from BASF under the designation OPPANOL B12. Other suitable polyisobutenes commercially available from BASF include, but are not limited to, OPPANOL Bll, B13, and B15. These materials have an average molecular weight of from about 45,000 to about 85,000. However, it will be appreciated that in no way is the present invention limited to the use of polyisobutenes having such molecular weights. Instead, the invention includes the use of polyisobutenes having molecular weights greater than or less than these values.

[0020] Examples of suitable styrene block type copolymers include, but are not limited to, various styrene isoprene materials. Styrenic block copolymers are widely used to make hot melt adhesives for a wide variety of uses. Hot melt adhesives based on styrenic block copolymers such as K ATON^® thermoplastic rubber provide excellent adhesion. Additionally, such styrenic block copolymer based adhesives maintain adhesion in elastically demanding applications.

[0021] A particularly preferred material for use as the styrene component is a blend of

80% styrene isoprene liquid rubber and 20% styrene isoprene rubber. All references to percentages are percentages by weight.

Low Water Activity Antimicrobial Matrix

[0022] The preferred embodiment compositions also comprise a low water activity antimicrobial matrix which is preferably honey. The term "water activity" refers to a measure of the free moisture in a substance. A "low water activity" as referred to herein refers to a level of water activity that is less than the level of activity generally required to support bacteria or other microbes. Thus, a low water activity limits growth of bacteria or other microbes, and thus has antimicrobial activity.

[0023] The term "matrix" refers to a substance comprising a material, agent, or plurality of agent(s) in which the material or agent(s) are embedded, enclosed, or otherwise contained in the substance.

[0024] The low water activity antimicrobial matrix is preferably in the form of honey as described in greater detail below.

Honey

[0025] Manuka honey is produced from bees who feed on the flowers of the Manuka bush, also known as the "Tea Tree". Manuka honey has anti-bacterial properties. Tea tree oil is commonly from the related Melaleuca tree native to Australia and is used as a topical antibiotic and antifungal for wounds that fail to close.

[0026] Manuka honey, produced when honeybees gather the nectar from the flowers of the Manuka bush, is distinctively flavored, darker and richer in taste than clover honey and has strong antibacterial and antifungal properties. The finest quality Manuka honey with the most potent antimicrobial properties is produced from hives placed in wild, uncultivated areas with abundant growth of Manuka bushes.

[0027] In addition to, or instead of Manuka honey, one or more other types of honey can be incorporated in an adhesive composition. For example, honey derivatives, artificial honey, or even a saturated sugar solution could be utilized. Generally, any honey or equivalent component which provides the various functions described herein and creates a sufficient amount of osmotic pressure to thereby support wound debridement can be utilized. Preferably, honeys that exhibit antimicrobial efficacy are preferred. In this regard, honey having at least 10% peroxide activity is preferred. The most preferred type of honey is Manuka honey.

Optional Components

[0028] In the event that one or more aqueous natural or synthetic gelling agents are utilized in the composition, various polyethylene glycols and/or carboxymethyl cellulose materials can be used. A representative preferred carboxymethyl cellulose material is commercially available from Ashland Aqualon under the designation AQUASO B A500. This material is sodium carboxymethyl cellulose (CMC). One or more polyethylene glycol (PEG) materials such as PEG 400 can be used. It will be understood that in no way is the invention limited to any of these noted materials. Instead, other carboxymethyl cellulose materials and/or polyethylene glycols can be used. Moreover, it is also contemplated that other gelling agents can be used in addition to or instead of those noted herein. The amount of the gelling agent(s) used in the compositions is any effective amount. Preferably, this amount is from about 0.1 part to about 30 parts relative to the amounts of the adhesive or rubber component and the low water activity matrix.

[0029] The composition may optionally also include effective amounts of one or more medicinal agents. A preferred example of such a medicinal agent is Lidocaine. Lidocaine (Xylocaine) or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery. Lidocaine is also known as 2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide. Non- limiting examples of one or more medicinal agents include for example, a sterilizer or disinfectant, a wound astringent healing promoter, a hemostatic agent, an anti-inflammatory agent, an antihistamine, and a local anesthetic. Specific examples of the sterilizer or disinfectant include chlorhexidine gluconate, benzalkonium chloride, chloroxylenol, acrinol, thianthol, dequalinium chloride, sulfisomidine, sulfamine, nitrofurazone, boric acid, homosulfamine, and triclocarban. Examples of the healing promoter include zinc oxide, pyridoxine hydrochloride, tocopherol acetate, and pyridoxine dipalmitate. Examples of the hemostatic agent include naphazoline hydrochloride, zinc sulfate, and ephedrine hydrochloride. Examples of the anti-inflammatory agent include steroids such as prednisolone, dexamethasone, cortisone acetate and other steroids, glycyrrhetinic acid, and lysozyme chloride. Examples of the antihistamine include chlorophenilamine maleate and diphenhydramine hydrochloride. Examples of the local anesthetic include lidocaine, ethyl aminobenzoate, procaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, and diethyl aminoethyl p-butylamino-benzoate hydrochloride. These are representative examples of medicinal agents. It will be appreciated that the invention is not limited in any fashion to any of these agents. The amount of the medicinal agent(s) used in the compositions is any effective amount. Preferably, this amount is from about 0.1 part to about 30 parts relative to the amounts of the adhesive or rubber component and the low water activity matrix.

Medical Articles

[0030] The present invention also provides a wide array of medical articles that utilize the compositions described herein. For example, the invention includes wound dressings, wound pads, bandages, gauze and gauze-based articles, and the like. Generally, any article that is attached to a user's skin and which is used for protecting that region, such as covering a wound or abrasion, can utilize one or more aspects of the invention. In addition, it is also contemplated that other adhesively attached articles for contacting a user's skin can utilize one or more aspects of the invention.

[0031] Specifically, the medical article is impregnated or otherwise provided with an effective amount of the preferred embodiment compositions described herein. The medical article enables and preferably maintains contact between the composition and a user's skin, and particularly a wound or other region in need of treatment.

[0032] The preferred embodiment honey based products can be utilized to effectively manage infected wounds when applied or used in conjunction with appropriate dressings. Honey based wound dressings have a number of features that enable their use as general chronic wound care dressings. These properties include osmotic absorption of excess exudate and inherent peroxide (antibacterial) activities which promote wound cleansing and wound bed oxygenation. Honey based wound dressings also provide beneficial nutrients to the wound bed.

[0033] In certain versions of the invention, it may be preferred to use a solid form of the composition. That is, the adhesive or rubber component and the low water activity antimicrobial matrix including honey can be appropriately combined along with any other agents as described herein, and then further dried or processed to provide a product in a solid or non-flowing form. A preferred solid composition is produced by extrusion and drying. The resulting product can be in the form of a thin layer or sheet which can be readily incorporated into a medical article.

[0034] It is also contemplated that the preferred embodiment compositions can be appropriately modified to serve as pressure sensitive adhesives. Such adhesives can be used in medical articles to provide a means of attaching the article to a user.

Methods

[0035] The preferred embodiment compositions can be prepared in several ways. A preferred technique is to blend the adhesive or rubber component of the composition with the honey. Preferably, an initial portion of the adhesive or rubber component is blended with the honey, and then one or more remaining portions of the adhesive or rubber component are blended therein. Alternatively, an initial portion of the honey is blended with the adhesive or rubber component, and then one or more remaining portions of the honey are blended therein. In still other alternate methods, initial portions of both honey and the adhesive or rubber component are blended together, and then one or more remaining portions of each are blended together.

[0036] Preferably, the honey or honey component of the composition is maintained at temperatures less than 50°C, more preferably less than 40°C, and more preferably less than 30°C. Most preferably, the honey component and/or any intermediate blend components are maintained at or about ambient temperatures. This reduces the potential for degradation of the honey. In addition, this promotes retention of antimicrobial properties of the honey. The composition can be prepared using conventional blending and processing components.

Examples

[0037] A series of formulations in accordance with the invention were prepared to further evaluate the properties and characteristics of the compositions. Specifically, formulations A-G having various proportions of the components described herein were formed. The amounts of each component are expressed in parts by weight. The component T2560 is a rubber adhesive comprising 80% styrene isoprene liquid rubber and 20% styrene isoprene rubber. The components were mixed together in three or four phases over the course of 30 minutes. All components were at ambient temperature or substantially so.

Table 1 - Formulation A

Honey Containing Adhesive

Table 2 - Formulation B

Honey Containing Adhesive

Table 3 - Formulation C

Honey Containing Adhesive

Table 4 - Formulation D Honey Containing Adhesive

Table 5 - Formulation E

Honey Containing Adhesive

Table 6 - Formulation F Honey Containing Adhesive

Table 7 - Formulation G

Honey Containing Adhesive

[0038] Each formulation A-G exhibited acceptable or excellent appearance, viscosity, and other properties such that each formulation could be readily incorporated in a medical article and/or used in a method for treating a wound or other region on a user's skin.

[0039] Many other benefits will no doubt become apparent from future application and development of this technology.

[0040] All patents, published applications, and articles noted herein are hereby incorporated by reference in their entirety.

[0041] It will be understood that any one or more feature or component of one embodiment described herein can be combined with one or more other features or components of another embodiment. Thus, the present invention includes any and all combinations of components or features of the embodiments described herein.

[0042] As described hereinabove, the present invention solves many problems associated with previously known compositions, practices and devices. However, it will be appreciated that various changes in the details, materials and arrangements of components or operations, which have been herein described and illustrated in order to explain the nature of the invention, may be made by those skilled in the art without departing from the principle and scope of the invention, as expressed in the appended claims.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A composition comprising:

from about 5 parts to about 55 parts of an adhesive or rubber component;

from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey.

2. The composition of claim 1 wherein the adhesive or rubber component includes one or more polyisobutene and/or styrene block type copolymers.

3. The composition of claims 1-2 wherein the honey is Manuka honey.

4. The composition of claims 1-3 further comprising:

one or more aqueous gelling agents.

5. The composition of claim 4 wherein the gelling agent is selected from the group consisting of polyethylene glycols, carboxymethyl cellulose materials, and combinations thereof.

6. The composition of claims 1-5 further comprising:

one or more medicinal agents.

7. The composition of claim 6 wherein the medicinal agent is selected from the group consisting of a sterilizer or disinfectant, a wound astringent healing promoter, a hemostatic agent, an anti-inflammatory agent, an antihistamine, a local anesthetic, and combinations thereof.

8. The composition of claim 7 wherein the sterilizer or disinfectant is selected from the group consisting of chlorhexidine gluconate, benzalkonium chloride, chloroxylenol, acrinol, thianthol, dequalinium chloride, sulfisomidine, sulfamine, nitrofurazone, boric acid, homosulfamine, triclocarban, and combinations thereof.

9. The composition of claim 7 wherein the healing promoter is selected from the group consisting of zinc oxide, pyridoxine hydrochloride, tocopherol acetate, pyridoxine dipalmitate, and combinations thereof.

10. The composition of claim 7 wherein the hemostatic agent is selected from the group consisting of naphazoline hydrochloride, zinc sulfate, and ephedrine hydrochloride, and combinations thereof.

11. The composition of claim 7 wherein the anti-inflammatory agent is selected from the group consisting of prednisolone, dexamethasone, cortisone acetate and other steroids, glycyrrhetinic acid, lysozyme chloride, and combinations thereof.

12. The composition of claim 7 wherein the antihistamine is selected from the group consisting of chlorophenilamine maleate, diphenhydramine hydrochloride, and combinations thereof.

13. The composition of claim 7 wherein the local anesthetic is selected from the group consisting of lidocaine, ethyl aminobenzoate, procaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethyl aminoethyl p-butylamino-benzoate hydrochloride, and combination thereof.

14. The composition of claim 13 wherein the local anesthetic is lidocaine.

15. The composition of claims 1-14 wherein the composition is a hydrocolloid.

16. The composition of claims 1-15 wherein the honey has at least 10% peroxide activity.

17. A medical article comprising a composition including from about 5 parts to about 55 parts of an adhesive or rubber component; and from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey.

18. The medical article of claim 17 wherein the article is selected from the group consisting of wound dressings, wound pads, bandages, gauze, gauze-based and articles.

19. The medical article of claims 17-18 wherein the adhesive or rubber component includes one or more polyisobutene and/or styrene block type copolymers.

20. The medical article of claims 17-19 wherein the honey is Manuka honey.

21. The medical article of claims 17-20 further comprising:

one or more aqueous gelling agents.

22. The medical article of claims 21 wherein the gelling agent is selected from the group consisting of polyethylene glycols, carboxymethyl cellulose materials, and combinations thereof.

23. The medical article of claims 17-22 further comprising:

one or more medicinal agents.

24. The medical article of claim 23 wherein the medicinal agent is selected from the group consisting of a sterilizer or disinfectant, a wound astringent healing promoter, a hemostatic agent, an anti-inflammatory agent, an antihistamine, a local anesthetic, and combinations thereof.

25. The medical article of claim 24 wherein the sterilizer or disinfectant is selected from the group consisting of chlorhexidine gluconate, benzalkonium chloride, chloroxylenol, acrinol, thianthol, dequalinium chloride, sulfisomidine, sulfamine, nitrofurazone, boric acid, homosulfamine, triclocarban, and combinations thereof.

26. The medical article of claim 24 wherein the healing promoter is selected from the group consisting of zinc oxide, pyridoxine hydrochloride, tocopherol acetate, pyridoxine dipalmitate, and combinations thereof.

27. The medical article of claim 24 wherein the hemostatic agent is selected from the group consisting of naphazoline hydrochloride, zinc sulfate, ephedrine hydrochloride, and combinations thereof.

28. The medical article of claim 24 wherein the anti-inflammatory agent is selected from the group consisting of prednisolone, dexamethasone, cortisone acetate and other steroids, glycyrrhetinic acid, lysozyme chloride, and combinations thereof.

29. The medical article of claim 24 wherein the antihistamine is selected from the group consisting of chlorophenilamine maleate diphenhydramine hydrochloride, and combinations thereof.

30. The medical article of claim 24 wherein the local anesthetic is selected from the group consisting of lidocaine, ethyl aminobenzoate, procaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethyl aminoethyl p-butylamino-benzoate hydrochloride, and combinations thereof.

31. The medical article of claim 30 wherein the local anesthetic is lidocaine.

32. The medical article of claims 17-31 wherein the composition is a hydrocolloid.

33. The medical article of claims 17-32 wherein the honey has at least 10% peroxide activity.

34. A method of forming a composition containing honey, the method comprising:

providing from about 5 parts to about 55 parts of an adhesive or rubber component;

providing from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey;

blending the adhesive or rubber component with the matrix including honey.

35. The method of claim 34 wherein the adhesive or rubber component includes one or more polyisobutene and/or styrene block type copolymers.

36. The method of claims 34-35 wherein the honey is Manuka honey.

37. The method of claims 34-36 further comprising:

providing one or more aqueous gelling agents; and

blending the one or more aqueous agents with at least one of the adhesive or rubber component and the matrix including honey.

38. The method of claim 37 wherein the gelling agent is selected from the group consisting of polyethylene glycols, carboxymethyl cellulose materials, and combinations thereof.

39. The method of claims 34-38 further comprising:

providing one or more medicinal agents; and

blending the one or more medicinal agents with at least one of the adhesive or rubber component and the matrix including honey.

40. The method of claims 34-39 wherein the honey is maintained at a temperature of less than 50°C.

41. The method of claims 34-39 wherein the honey is maintained at a temperature of less than 40°C.

42. The method of claims 34-39 wherein the honey is maintained at a temperature of less than 30°C.

43. The method of claims 34-39 wherein the honey is maintained at ambient temperature.

44. A method for treating a wound comprising:

providing a medical article including from about 5 parts to about 55 parts of an adhesive or rubber component, and from about 5 parts to about 45 parts of a low water activity antimicrobial matrix including honey;

applying the medical article over the wound.