NZ629152B - Compostions of honey and glycerine - Google Patents
Compostions of honey and glycerineInfo
- Publication number
- NZ629152B NZ629152B NZ629152A NZ62915214A NZ629152B NZ 629152 B NZ629152 B NZ 629152B NZ 629152 A NZ629152 A NZ 629152A NZ 62915214 A NZ62915214 A NZ 62915214A NZ 629152 B NZ629152 B NZ 629152B
- Authority
- NZ
- New Zealand
- Prior art keywords
- honey
- composition
- glycerine
- kanuka
- phenol
- Prior art date
Links
- 235000012907 honey Nutrition 0.000 title claims abstract description 200
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 title claims abstract description 72
- 235000011187 glycerol Nutrition 0.000 title claims abstract description 72
- 239000000203 mixture Substances 0.000 claims abstract description 132
- 235000017763 Leptospermum ericoides Nutrition 0.000 claims abstract description 53
- 201000004700 rosacea Diseases 0.000 claims abstract description 37
- 241001303601 Rosacea Species 0.000 claims abstract description 32
- 208000006641 Skin Disease Diseases 0.000 claims abstract description 26
- 230000000694 effects Effects 0.000 claims abstract description 23
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 206010000496 Acne Diseases 0.000 claims abstract description 12
- 206010012444 Dermatitis diaper Diseases 0.000 claims abstract description 12
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 9
- 229940076185 Staphylococcus aureus Drugs 0.000 claims abstract description 9
- 230000000699 topical Effects 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 2
- 241001514640 Tristaniopsis laurina Species 0.000 claims 4
- 208000009889 Herpes Simplex Diseases 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 244000062939 Leptospermum ericoides Species 0.000 abstract description 49
- 241000700588 Human alphaherpesvirus 1 Species 0.000 abstract description 10
- 241000701074 Human alphaherpesvirus 2 Species 0.000 abstract description 10
- 240000003553 Leptospermum scoparium Species 0.000 abstract description 8
- 235000016887 Leptospermum scoparium Nutrition 0.000 abstract description 8
- NJTGANWAUPEOAX-UHFFFAOYSA-N MolPort-023-220-454 Chemical compound OCC(O)CO.OCC(O)CO NJTGANWAUPEOAX-UHFFFAOYSA-N 0.000 abstract 1
- 238000009472 formulation Methods 0.000 description 21
- 210000003491 Skin Anatomy 0.000 description 11
- 208000001688 Herpes Genitalis Diseases 0.000 description 7
- 206010067152 Oral herpes Diseases 0.000 description 7
- 201000004946 genital herpes Diseases 0.000 description 7
- 238000003306 harvesting Methods 0.000 description 7
- 241000257303 Hymenoptera Species 0.000 description 6
- 231100000494 adverse effect Toxicity 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- AIJULSRZWUXGPQ-UHFFFAOYSA-N pyruvic aldehyde Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 6
- 231100000247 serious adverse effect Toxicity 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 229940079593 drugs Drugs 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 200000000019 wound Diseases 0.000 description 5
- 238000003860 storage Methods 0.000 description 4
- 206010046736 Urticarias Diseases 0.000 description 3
- 230000000844 anti-bacterial Effects 0.000 description 3
- 230000000975 bioactive Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000009928 pasteurization Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 230000003115 biocidal Effects 0.000 description 2
- 230000000295 complement Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-Dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- BDJRBEYXGGNYIS-UHFFFAOYSA-N Azelaic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 1
- 244000144987 Brood Species 0.000 description 1
- 208000001590 Congenital Abnormality Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 229940064701 Corticosteroid nasal preparations for topical use Drugs 0.000 description 1
- 229960001334 Corticosteroids Drugs 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 108060003189 GLE1 Proteins 0.000 description 1
- NOEGNKMFWQHSLB-UHFFFAOYSA-N Hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229960000282 Metronidazole Drugs 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 206010037888 Rash pustular Diseases 0.000 description 1
- 230000002730 additional Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 201000005794 allergic hypersensitivity disease Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000845 anti-microbial Effects 0.000 description 1
- 238000003556 assay method Methods 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001332 colony forming Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 201000009910 diseases by infectious agent Diseases 0.000 description 1
- 230000001815 facial Effects 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000003898 horticulture Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial Effects 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000241 respiratory Effects 0.000 description 1
- 230000000717 retained Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001954 sterilising Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000002522 swelling Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940083878 topical for treatment of hemorrhoids and anal fissures Corticosteroids Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000003442 weekly Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L21/00—Marmalades, jams, jellies or the like; Products from apiculture; Preparation or treatment thereof
- A23L21/20—Products from apiculture, e.g. royal jelly or pollen; Substitutes therefor
- A23L21/25—Honey; Honey substitutes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
- A61K35/644—Beeswax; Propolis; Royal jelly; Honey
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/987—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
- A61K8/988—Honey; Royal jelly, Propolis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Abstract
Disclosed is a honey composition comprising 85-95% honey by weight, and 5-15% glycerine (glycerol) by weight, wherein the honey is selected from kanuka and manuka honey. Glycerine is added to the composition to achieve stable viscosity of over a temperature range of 4-35 °C. The compositions have a total activity measured against Staphylococcus aureus NZRM 87 (ATCC 9144) expressed as equivalent % phenol, of at least about 18% phenol. Also disclosed is the use of the honey composition for treating or preventing a skin disorder selected group consisting of acne, nappy rash, rosacea, and herpes simplex virus 1 or 2. total activity measured against Staphylococcus aureus NZRM 87 (ATCC 9144) expressed as equivalent % phenol, of at least about 18% phenol. Also disclosed is the use of the honey composition for treating or preventing a skin disorder selected group consisting of acne, nappy rash, rosacea, and herpes simplex virus 1 or 2.
Description
COMPOSTIONS OF HONEY AND GLYCERINE
FIELD OF INVENTION
This invention relates generally to compositions comprising kanuka honey and glycerine,
methods for preparing such compositions and their uses.
BACKGROUND
Honey has been used for centuries to treat skin conditions and is known historically for its
effectiveness in the treatment of wounds and burns.
In recent times, manuka honey, in particular, has received attention for its reported
antibacterial activity. This honey is produced by bees who harvest the nectar of
Leptospermum scoparium. The antibacterial activity of manuka honey has been labelled the
“Unique Manuka Factor” (UMF) and it has been reported that the UMF derives from the
presence of methylglyoxal in the honey.
describes medicinal compositions containing honey derived from
Leptospermum scoparium and their use in treating ophthalmic, respiratory or otic conditions
caused by microbial infections.
Kanuka honey, on the other hand, is a bio-active honey that is less well-known than
manuka honey. It is produced by bees who harvest the nectar of the kanuka (Kunzea
ericoides) and has been found to have anti-microbial activity against Staphylococcus
aureus. Furthermore, raw kanuka honey has been reported to have methylglyoxal levels of
about 1024 mg/kg and medical grade kanuka honey has been reported to have
methylglyoxal levels of 1154 mg/kg (S Holt et al., The Journal of Complementary and
Alternative Medicine, (2012) 18(3), 203-204).
There are difficulties associated with the use of honey as a skin treatment. Honey itself is
sticky and strong smelling. The consistency of honey varies with temperature. For example,
at room temperature honey might be a of suitable consistency for application to the skin,
but at lower temperatures, such as a normal household refrigeration temperature of about 4
°C, honey can become hard and can crystallise, which reduces its ease of use and appeal to
users. In warmer conditions, its viscosity decreases and honey can become too “runny” for
application to skin.
Some efforts have been made in formulating honeys, e.g. for wound treatment. NZ 542258
describes a manuka honey composition for treating wounds. The composition includes a
viscosity increasing agent which increases, or at least maintains, the viscosity of the
composition after application to a wound. NZ501687 describes a wound dressing
composition that includes honey and one or more gelling agents, such as alginate-based
materials.
However, while formulating honey with other additives might address some of the
difficulties associated with using honey as a skin treatment, dilution of the honey can result
in the loss of its particular biological activity (e.g. see S Holt et al., The Journal of
Complementary and Alternative Medicine, (2012) 18(3), 203-204).
There is therefore a need for honey compositions that are stable at a variety of
temperatures, and wherein the honey retains its biological activity.
It is an object of the invention to provide a composition comprising kanuka honey and
glycerine, and methods for preparing such compositions, that overcome some of these
problems, or to at least provide a useful alternative.
STATEMENTS OF INVENTION
In a first aspect, the invention provides a honey composition comprising:
from about 85% w/w honey to about 95% w/w honey; and
from about 5% w/w glycerine to about 15% w/w glycerine;
wherein the honey is kanuka honey
In a second aspect the invention provides a method of preparing a honey composition
including the step of admixing kanuka honey with glycerine, at a ratio of honey to glycerine
of about 85% honey : 15% glycerine to about 95% honey : 5% glycerine (w/w).
Preferably the honey is medical grade kanuka honey.
Preferably the honey composition comprises about 90% w/w honey and about 10% w/w
glycerine.
Preferably the honey composition is substantially free of other components. Alternatively,
the honey composition may further comprise one or more additional components.
In a further aspect, the invention provides a honey composition comprising:
kanuka honey and glycerine in a ratio of about 85:15 to about 95:5 honey to glycerine; and
one or more additional components.
Preferably the ratio of honey to glycerine is about 90:10 honey to glycerine. The one or
more additional components may be, for example, one or more bio-active compounds, e.g.
one or more drug compounds. The one or more additional components may be, for
example, one or more medicaments useful for treating a skin disorder.
It is further preferred that the honey composition is stable when stored at temperatures
below room temperature, e.g. between about 4 °C and about 10 °C, e.g. at a temperature
of about 4 °C, for up to 8 days. It is also preferred that sugars present in the honey
composition do not crystallise when the honey composition is stored at temperatures below
room temperature, e.g. between about 4 °C and about 10 °C, e.g. at a temperature of
about 4 °C, for up to 8 days.
It is further preferred that the honey composition has stable bio-activity when stored at
temperatures above room temperature, e.g. between about 20 °C and about 35 °C, e.g. at
temperatures of about 35 °C, for up to 15 days.
It is further preferred that the honey composition has a total activity against Staphylococcus
aureus NZRM 87 (ATCC 9144), and expressed as equivalent % phenol, of at least about
18% phenol, preferably at least about 21% phenol, more preferably about 21-22% phenol,
most preferably about 21.8% phenol.
Preferably the honey is medical grade kanuka honey.
Preferably the ratio of honey to glycerine is about 90% honey : 10% glycerine (w/w).
The invention also provides a stable honey composition produced according to the method
of the third aspect of the invention. It is preferred that the stable honey composition is
stable when stored at temperatures between about 4 °C and about 10 °C, e.g. at a
temperature of about 4 °C, for up to 8 days. It is also preferred that sugars present in the
stable honey composition do not crystallise when the honey composition is stored at
temperatures between about 4 °C and about 10 °C, e.g. at a temperature of about 4 °C, for
up to 8 days. It is further preferred that the stable honey composition is stable when stored
at temperatures between about 20 °C and about 35 °C, e.g. at temperatures of about 35
°C, for up to 15 days.
It is further preferred that the honey composition has a total activity against Staphylococcus
aureus NZRM 87 (ATCC 9144), and expressed as equivalent % phenol, of at least about
19% phenol, preferably at least about 21% phenol, more preferably about 21-22% phenol,
most preferably about 21.8% phenol.
In another aspect, the invention provides a topical preparation comprising a honey
composition as defined above.
In still another aspect, the invention provides a tube containing a honey composition as
defined above.
In still another aspect, the invention provides a jar containing a honey composition as
defined above.
In still another aspect, the invention provides a honey composition as defined above for use
as a medicament.
In yet another aspect the invention provides the use of an effective amount of kanuka
honey in the manufacture of a honey composition of the invention for treating or preventing
a skin disorder. Preferably the kanuka honey is medical grade kanuka honey. Preferably the
skin disorder is selected from the group consisting of acne, nappy rash and rosacea.
Alternatively preferably the skin disorder is caused by herpes simplex virus 1 or 2. Still
more preferably the skin disorder is rosacea. Alternatively preferably the skin disorder is
genital herpes or oral herpes.
In yet a further aspect of the present invention there is provided a kit for treating or
preventing a skin disorder, the kit comprising honey and glycerine together with instructions
for treating or preventing the skin disorder.
Preferably the skin disorder is selected from the group consisting of acne, nappy rash and
rosacea. Alternatively preferably the skin disorder is caused by herpes simplex virus 1 or 2.
Still more preferably the skin disorder is rosacea. Alternatively preferably the skin disorder
is genital herpes or oral herpes.
A honey composition as defined above is referred to herein as a “composition of the
invention”.
DETAILED DESCRIPTION
The present invention provides novel kanuka honey compositions comprising kanuka honey
and glycerine. The honey compositions of the invention are surprisingly stable even when
stored at temperatures lower or higher than room temperature (e.g. even at normal
household refrigeration temperatures). Advantageously, as shown in Example 2,
compositions of the invention comprising kanuka honey retain their activities, as measured
against Staphylococcus aureus NZRM 87 (ATCC 9144) and expressed as the equivalent %
phenol.
The compositions of the invention are readily prepared by admixing honey, such as honey
produced by bees who harvest the nectar of Kunzea ericoides, with glycerine. The preferred
relative amounts of the honey and glycerine components range from about 85% w/w honey
: 15% w/w glycerine to about 95% w/w honey : 5% w/w glycerine, preferably about 90%
w/w honey : 10% w/w glycerine, based on the total amount of ingredients. However, the
invention also includes compositions comprising about 85% w/w honey : 15% w/w
glycerine, about 86% w/w honey : 14% w/w glycerine, about 87% w/w honey : 13% w/w
glycerine, about 88% w/w honey : 12% w/w glycerine, about 89% w/w honey : 11% w/w
glycerine, about 91% w/w honey : 9% w/w glycerine, about 92% w/w honey : 8% w/w
glycerine, about 93% w/w honey : 7% w/w glycerine, about 94% w/w honey : 6% w/w
glycerine or about 95% w/w honey : 5% w/w glycerine, based on the total amount of
ingredients. The composition is preferably substantially free of other components.
The compositions of the invention provide the advantage that the biological activity of the
honey is retained, even though the honey is diluted by admixing with glycerine. In some
preferred embodiments of the invention, the biological activity of a composition of the
invention (e.g. a composition comprising 90% w/w medical grade kanuka honey : 10% w/w
glycerine) has at least about 75%, more preferably at least about 80% and still more
preferably at least about 85%, e.g. about 86-87% of the biological activity of 100% medical
grade kanuka honey.
Those skilled in the art will realise that it is sometimes preferable to purify raw honey, for
example where the honey is to be used in topical formulations, so that it is free from
impurities that can cause undesirable inflammatory reactions in users. Thus, kanuka honey
is preferably purified by filtration, e.g. through a 50 micron filter, and either pasteurisation
or gamma irradiation, before being admixed with glycerine to form a composition of the
invention. Preparative Example 1 describes how raw kanuka honey can be collected and
purified.
Those skilled in the art will also understand that the glycerine used in the compositions of
the invention can be any suitable glycerine, such as food grade glycerine (e.g. about 99.7+
% pure food grade glycerine).
The honey compositions of the invention are stable when stored at temperatures below
room temperature, e.g. between about 4 °C and about 10 °C, e.g. between about 5 °C and
about 9 °C, e.g. between about 6 °C and about 8 °C, for up to 8 days, e.g. up to 7 days, up
to 6 days, up to 5 days or up to 4 days. For example, the honey compositions of the
invention can be stored at a temperature of about 4 °C, for up to 8 days, e.g. up to 7 days,
up to 6 days, up to 5 days or up to 4 days. It is also preferred that sugars present in the
honey composition do not crystallise when the honey composition is stored at temperatures
below room temperature, e.g. between about 4 °C and about 10 °C, e.g. at a temperature
of about 4 °C, for up to 8 days, e.g. up to 7 days, up to 6 days, up to 5 days or up to 4
days.
It is further preferred that the honey composition is stable when stored at temperatures
above room temperature, e.g. between about 20 °C and about 35 °C, e.g. between about
21 °C and about 34 °C, e.g. between about 22 °C and about 33 °C, e.g. between about 23
°C and about 32 °C, e.g. between about 24 °C and about 31 °C, e.g. between about 25 °C
and about 30 °C, e.g. between about 26 °C and about 29 °C, e.g. between about 27 °C and
about 28 °C, e.g. for up to 13 days, up to 10 days, up to 8 days or up to 5 days. For
example, the honey compositions of the invention can be stored at a temperature of about
°C, for up to 15 days, e.g. up to 13 days, up to 10 days, up to 8 days or up to 5 days.
The honey compositions of the invention are useful for the treatment of skin conditions such
as acne, nappy rash, rosacea, and those caused by herpes simplex virus 1 or herpes
simplex virus 2 (e.g. genital or oral herpes). For example, Example 3 describes a clinical
trail of a composition of the invention (comprising 90% w/w medical grade kanuka honey
and 10% w/w glycerine) for the treatment of rosacea. The primary outcome measure of the
trial is the proportion of subjects who have a ≥2 improvement in an investigator-rated 7
point Rosacea Severity Score (RSS) at week 8 of the trial compared to baseline. The results
show that 17.4% of patients in the control group have a more than or equal to two point
change in RSS at week 8 from baseline. In contrast, 34.3% of patients in the group
receiving a composition of the invention have a more than or equal to two point change in
RSS at week 8 from baseline. (Relative risk composition of the invention versus control:
2.03 (95% CI 1.11 to 3.72), P=0.020.). Thus, the composition of the invention provides a
clinically and statistically significant improvement in RSS versus control.
Those skilled in the art will understand that the honey compositions of the invention may
also comprise one or more additional components, such as one or more bio-active
components, e.g. drug compounds or components that are useful for treating a skin
disorder. Such compositions comprise honey and glycerine in a ratio of about 85:15 to
about 95:5 honey to glycerine, preferably about 90:10 honey to glycerine. In other words, a
honey composition of the invention may be a base with which one or more additional
component(s) is combined. It will be clear to those skilled in the art that, in such
compositions, the ratio of honey to glycerine is about 85:15 to about 95:5 honey to
glycerine. For example, a composition of the invention comprising honey and glycerine in a
ratio 90:10 honey to glycerine may further comprise one or more drug compounds.
Those skilled in the art will also realise that the honey compositions of the invention can be
administered to patients in a number of ways. For example, the compositions can be
administered topically, e.g. for the treatment of skin conditions such as acne, nappy rash,
rosacea, and those caused by herpes simplex virus 1 or herpes simplex virus 2 (e.g. genital
or oral herpes). Alternatively, the compositions can be administered orally.
Typically, for topical treatment of skin disorders such as acne, rosacea, nappy rash, or those
caused by herpes simplex virus 1 or herpes simplex virus 2 (e.g. genital or oral herpes), a
composition of the invention is applied directly to the skin, in an amount sufficient to cover
the area to be treated. A composition of the invention can be applied in this way up to 10
times per day, but more preferably about 1 to 5 times a day, and most preferably twice a
day.
For the topical treatment of rosacea, the composition of the invention is applied to the
affected area up to five times a day, preferably twice a day. Typically, the composition is
applied for 30-60 minutes per application.
Alternatively, a kanuka honey is useful for the treatment of skin conditions and can be
administered to patients topically, e.g. for the treatment of skin conditions such as acne,
nappy rash, rosacea, or those caused by herpes simplex virus 1 or herpes simplex virus 2.
Typically, for topical treatment of skin disorders such as acne, rosacea, nappy rash, or those
caused by herpes simplex virus 1 or herpes simplex virus 2 (e.g. genital or oral herpes), a
kanuka honey is applied directly to the skin, in an amount sufficient to cover the area to be
treated. A kanuka honey can be applied in this way up to 10 times per day, but more
preferably about 1 to 5 times a day, and most preferably twice a day. For the topical
treatment of rosacea, the kanuka honey is applied to the affected area up to five times a
day, preferably twice a day. Typically, the kanuka honey is applied for 30-60 minutes per
application.
The compositions of the invention can be conveniently packaged into any suitable receptacle
such as a tube, jar or other container, for use by consumers. Because of their stability, the
compositions are suitable for storage at a range of temperatures in said receptacles.
The present invention also relates to devices and kits for treating skin disorders. Suitable
kits comprise honey and glycerine sufficient for at least one treatment of at least one skin
disorder, for separate, sequential or simultaneous use, together with instructions for
performing the treatment/prevention. Preferably the skin disorder is selected from the
group consisting of acne, nappy rash, rosacea, and those caused by herpes simplex virus 1
or herpes simplex virus 2 (e.g. genital or oral herpes).
The instructions for use of the kit and treating/preventing the skin disorder can be in the
form of labelling, which refers to any written or recorded material that is attached to, or
otherwise accompanies a kit at any time during its manufacture, transport, sale or use. For
example, the term “labelling” encompasses advertising leaflets and brochures, packaging
materials, instructions, audio or video cassettes, computer discs, as well as writing
imprinted directly on kits.
Definitions
The term “kanuka honey” refers to honey produced by bees that harvest the nectar of
Kunzea ericoides.
The term “medical grade kanuka honey” refers to honey produced by bees that harvest the
nectar of Kunzea ericoides, which honey has been purified. Purification may be effected by
filtration, e.g. through a 50 micron filter, and either pasteurisation or gamma irradiation.
The term “patient” includes human and non-human animals. Non-human animals include,
but are not limited to, birds and mammals.
The terms “treatment” and the like refer to preventing, curing, delaying the onset of, or
ameliorating a disease, disorder or condition, and/or reducing at least a symptom of such
disease, disorder or condition, for example reducing pain and/or irritation and/or
inflammation and/or swelling and/or redness and/or papules and/or pustules and/or
flakiness.
Any reference or discussion in relation to prior art publications within this specification does
not constitute an admission that such references form part of the common general
knowledge in the art in any country or jurisdiction.
Throughout the description and the claims, the words “comprise”, “comprising” and the like,
are intended to be interpreted in an inclusive sense and not an exclusive or exhaustive
sense, that is to say, “including, but not limited to”.
EXAMPLES
The invention is further described with reference to the following examples. It will be
appreciated that the invention as claimed is not intended to be limited in any way by these
examples.
Preparative Example 1: Medical Grade Honey
Kanuka honey is sourced from kanuka (Kunzea ericoides) and processed to medical grade
as follows:
Harvest protocol:
Hives are located a minimum of 10 km from any intensive horticulture.
Hives have GPS location recorded.
All honey batches can be traced to site origin.
All hives are inspected by a certified apiarist.
Extraction protocol:
All bees are removed prior to extraction.
Top and bottom bars of the frames are scraped and removed.
Wax cappings of the frames are pierced to eliminate wax contamination.
All frames are inspected to ensure absence of pollen cells.
All frames are inspected to ensure absence of brood cells.
Comb is pricked and honey extracted under pressure.
Honey is micro filtered to 50 microns.
Temperatures are maintained below 30 °C throughout production cycle.
Complies with New Zealand Food Safety Authority Risk assessment of harvesting and
extraction process.
Assay protocol/honey content:
Mono-floral purity >55% - (kanuka pollen count exceeds 55% under compound
microscopic analysis).
Foreign matter < 50 microns.
Crystallization < 50 microns.
Microbiology < 10 colony-forming units/g.
Hydroxymethylfurfural < 10 mg/kg.
Para-dichlorobenzene: zero tolerance.
Antibiotic contamination: zero tolerance.
Water content < 17%.
pH < 3.9.
Sterilization
All honey is sterilized at apiary using high temperature pasteurization.
Example 1: Temperature Stability of Honey/Glycerine Composition
Two honey compositions are tested:
Formulation 1: 100% medical grade kanuka honey
Formulation 2 (prepared by admixing medical grade kanuka honey with glycerine): 90%
w/w medical grade kanuka honey : 10% w/w glycerine
Samples of Formulation 1 and formulation 2 are stored at 4 °C for up to 8 days, 20 °C for
up to 6 months and 35 °C for up to 15 days and their consistencies are then assessed.
Results are shown in Table 1. The viscosity of formulation 1 decreases (relative to the
formulation’s viscosity at 20 °C) upon storage at 35 °C, and increases (relative to the
formulation’s viscosity at 20 °C) upon storage at 4 °C. The viscosity of formulation 2 is
substantially similar upon storage at all temperatures (4 °C, 20 °C, 35 °C).
Table 1: Consistencies of honey compositions
Formulation Consistency at 4 °C Consistency at 20 °C Consistency at 35 °C
Formulation 1 Hard, crystallised Good Runny
(more viscous) (less viscous)
Formulation 2 Good Good Good
Example 2: Activity of Honey/Glycerine Composition
Four honey compositions are tested:
Formulation 1: 100% medical grade kanuka honey
Formulation 2 (prepared by admixing kanuka honey with glycerine): 90% w/w medical
grade kanuka honey : 10% w/w glycerine
Formulation 3 (prepared by admixing kanuka honey with Bio-Cert gel (Dehydroxanthan
Gum Powder)): 40% w/w Bio-Cert gel (Dehydroxanthan Gum Powder) : 60% w/w medical
grade kanuka honey
Formulation 4 (prepared by admixing kanuka honey with glycerine): 40% w/w glycerine :
60% w/w medical grade kanuka honey.
Each formulation is tested for the Total Activity of the honey, i.e. the combination of the
hydrogen peroxide (H 0 ) found in ordinary honeys.
This is conducted by application of the testing methods of Hills Labs and/or NZ Labs, that
test for Total Activity (% of phenol), using the University of Waikato’s Honey Assay Method
(K. L. Allen, P. C. Molan, and G. M. Reid. A survey of the antibacterial activity of some
New Zealand honeys. Journal of pharmacy and pharmacology 43.12 (1991): 817-822). The
Total Activity is measured using Staphylococcus aureus NZRM 87 (ATCC 9144) and
expressed as the equivalent % phenol.
Results are shown in Table 2.
Table 2: Activities of honey compositions
Formulation Total Activity (% phenol)
Formulation 1 25.2
Formulation 2 21.8
Formulation 3 <8.2
Formulation 4 <8.2
Example 3: Clinical Trial for Rosacea
Study Design
Parallel group randomised controlled trial with assessor blinding.
Randomisation and Blinding:
Subjects and some staff at the study sites are not blinded to the treatment allocation. An
independent investigator at each site remains blinded to the treatment allocation
throughout the study and performs the RSS assessment.
Treatment allocation is randomised using a computer generated sequence. Subjects are
randomised in a 1:1 ratio to one of the following regimens:
1. Application of a composition comprising topical kanuka honey and food grade glycerine
combination, twice daily.
2. Application of a control cream (liquid paraffin and white soft paraffin topical emollient,
Ultrabase®), twice daily.
Investigational Product:
The Investigational Product is topical medical grade kanuka honey and food grade glycerine
(90% w/w honey: 10% w/w glycerine; a composition of the invention), packaged in 100 ml
plain tubes. Subjects are provided with a sufficient amount of the Investigational Product,
and apply an appropriate amount to the affected area twice daily for 30-60 minutes per
application, for eight weeks. The treatment may then be removed with warm water as
desired. Subjects may continue to use their usual medication, subject to the exclusion
criteria. The plain 100 ml tubes are labelled according to Good Manufacturing Practice
guidelines, for clinical trial use only.
Control Cream:
The control cream is a liquid paraffin and white soft paraffin topical emollient (Ultrabase®).
Subjects apply topical control cream to the affected area twice daily for 30-60 minutes per
application, for eight weeks.
The control cream is labelled according to Good Manufacturing Practice guidelines, for
clinical trial use only.
Subject diaries are used to capture each subject’s individual use of intervention, from Visit 1
until Visit 2. There are four trial sites
Study Subjects:
136 patients aged 16 or over with a doctor’s diagnosis of rosacea on the face. Subjects may
be identified at the time of first presentation or, with their primary care practitioner’s
consent, from the practice database, or by public advertisement.
Inclusion Criteria:
- Aged 16 or over at the time of enrolment
- Baseline facial Rosacea severity score (RSS) of ≥2
Exclusion criteria:
- Requirement for topical or systemic corticosteroids, as judged by treating doctor
- Requirement for antibiotic therapy, as judged by treating doctor
- Known or suspected allergy to honey or control cream
- Any other condition which, at the investigator’s discretion, it is believed may present
a safety risk or impact the feasibility of the study or the study results
Study Procedures and Treatments
Recruitment and Consent:
Potentially eligible patients are identified at the time of presentation to their primary care
practitioner, or via the practice database, or in public advertisement. Patients presenting
with mild to moderate rosacea and who potentially meet inclusion and exclusion criteria, are
offered the opportunity of taking part in the study.
Duration of intervention:
Subjects apply their randomised intervention twice daily for eight weeks. They attend for 3
visits in total; Baseline, Visit 2 and Visit 3.
Study Visits:
Consent, screening, baseline measurements and randomisation are completed at Visit 1
(Week 0). The response is assessed at Visit 2 (Week 2) and Visit 3 (Week 8).
Table 3: Schedule of Assessments
Visit number Visit 1 Visit 2 Visit 3
Time point Week 0 Week 2 Week 8
Day 1 Day 14 Day 56
Informed consent x
Eligibility criteria checked x
Demographics and medical x
history
Randomisation x
Administer DLQI x x x
Administer RSS x x x
Subject severity VAS x x
completion
Subject rated improvement x x
VAS completion
Provision of subject diary x
Collection of subject diary x
Safety monitoring x x x
RSS is administered by the blinded investigator
Severity VAS is completed daily from Visit 1 until Visit 2, within the subject diary.
DLQI: Dermatology Life Quality Index
VAS: Visual Analogue Score
Visit 1 (baseline visit):
Recruitment and consent procedures are completed. A second investigator blinded to
treatment allocation performs the baseline RSS. The subject completes a DLQI and VAS for
overall rosacea severity. The subject is randomised into the study, and the procedure for
applying the allocated treatment is explained to the subject. A ‘subject diary’ is provided to
the subject and they are instructed on how to complete it. The subject enters information
daily on application of the treatment and completes a subjective assessment of Rosacea
severity by VAS, from the baseline visit until the Week 2 visit.
Visit 2:
The subject’s diary is collected at visit 2 (week 2) and reviewed for completeness. The
subject is asked if they have experienced any adverse effects, which will be recorded and
reported as per the ‘Safety Monitoring’ section. The subject completes a Rosacea severity
VAS and the DLQI. Narrative feedback is also recorded. The subject completes the subject
rated improvement VAS. The second investigator blinded to treatment allocation performs
the RSS (this is the same investigator that performed the original assessments).
Visit 3 (final visit):
The subject is asked if they have experienced any adverse effects, which will be recorded
and reported as per the ‘Safety Monitoring’ section. The subject completes a Rosacea
severity VAS and the DLQI. Narrative feedback is also recorded. The subject completes the
subject rated improvement VAS. The second investigator blinded to treatment allocation
performs the RSS1 (this is the same investigator that performed the original assessments).
Study Visit Windows:
Each visit is conducted as close as possible to the scheduled date. If this is not possible then
Visit 2 may be conducted on Day 14 ±3 days, and Visit 3 may be conducted on Day 56 ±7
days.
Post trial handling:
Subjects revert to usual care under their primary care practitioner.
Outcome Measures
Primary:
The proportion of subjects who have a ≥2 improvement in investigator-rated 7 point
Rosacea Severity Score (RSS) at week 8 compared to baseline.
Secondary:
Change in subject-rated rosacea related quality of life, using the Dermatology Life
Quality Index (DLQI), at weeks 2 and 8 compared to baseline.
Subject-rated global rosacea improvement using a Visual Analogue Score (VAS) at
weeks 2 and 8
Change in subject-rated global rosacea severity using Visual Analogue Score (VAS)
at week 2 compared to baseline.
Change in investigator-rated 7 point RSS at Week 2 and Week 8 compared to
baseline.
Daily self-reported use (applications per day).
Weekly self-reported global rosacea severity (VAS scale).
Withdrawals due to worsening of rosacea.
Table 4: Trial Results
Primary outcome
Proportion with a ≥2 improvement in RSS Relative risk composition of the invention
at week 8 compared to baseline versus control: 2.03 (95% CI 1.11 to
3.72), P = 0.020
Secondary outcomes
Subject-rated rosacea improvement using composition of the invention minus control
a VAS at week 2 9.1 (3.5 to 14.7), P = 0.002
Subject-rated rosacea improvement using composition of the invention minus control
a VAS at week 8 12.3 (5.7 to 18.9)¸ P < 0.001
Change in subject-rated rosacea severity composition of the invention minus control
using VAS at week 2 compared to -8.2 (-13.9 to -2.5), P = 0.005
baseline
Change in RSS at week 2 compared to composition of the invention minus control,
baseline Hodges-Lehman estimate, -1 (-1 to 0), P =
0.03
Change in RSS at week 8 compared to composition of the invention minus control,
baseline Hodges-Lehman estimate, -1 (-1 to 0), P =
0.005
Withdrawals due to worsening 9/69 (13.0%) in the control group, 3/68
(4.4%) in the composition of the invention
group
Safety Monitoring
Adverse Events:
An adverse event is any untoward medical occurrence in a study subject temporally
associated with participation in the trial and the administration of study medication, whether
or not considered related to the medicine. An adverse event can therefore be any
unfavourable and unintended sign, symptom or disease temporally associated with the use
of the study treatment.
Adverse event data is collected and analysed with efficacy data at the end of the study.
Serious adverse events are notified to the ethics committee according to standard
guidelines. AEs and SAEs will be followed up until resolution, or until judged permanent.
Serious Adverse Events (SAEs):
For the purposes of this study the following events are considered to be SAEs:
- Death
- Life-threatening event
- Permanently disabling or incapacitating event
- Hospitalisation or prolongation of hospitalisation. Hospitalisation for the purposes of
SAE reporting is defined as an admission to hospital and does not include a
presentation to the Emergency Department followed by discharge without admission
or an admission for elective reasons
- Any event considered serious by the study investigator
Reporting of SAEs to the Ethics Committee takes place in accordance with the conditions of
ethical approval for the study.
Pregnancy itself is not regarded as an SAE. Any congenital anomaly or birth defect is
considered to be an SAE.
General Health Care
Participants receive usual general practitioner care during the study.
Power and Statistical Methods
Sample size and study power:
136 participants allows for a 10% drop-out rate. Analysis of 124 participants provides at
least 80% power at 5% significance to detect a 25% difference in response rates between
the groups.
References
Elewski, Boni E., Alan B. Fleischer Jr and David M. Pariser "A comparison of 15% azelaic
acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea:
results of a randomized trial" Archives of dermatology 139.11 (2003): 1444.
Finlay, A.Y. and Khan, G.K. “Dermatology Life Quality Index (DLQI) – a simple practical
measure for routine clinical use” Clin Exp Dermatol. 1994; 19: 210-216.
Where the foregoing description reference has been made to integers having known
equivalents thereof, those equivalents are herein incorporated as if individually set forth.
Although the invention has been described in connection with specific preferred
embodiments, it should be understood that the invention as claimed should not be unduly
limited to such specific embodiments.
It is appreciated that further modifications may be made to the invention as described
herein without departing from the spirit and scope of the invention.
INDUSTRIAL APPLICABILITY
The invention relates to compositions comprising honey and glycerine, methods for
preparing such compositions and their use for the treatment or prevention of skin diseases
such as acne, rosacea or nappy rash.
Claims (24)
1. A honey composition comprising: from about 85% w/w honey to about 95% w/w honey; and 5 from about 5% w/w glycerine to about 15% w/w glycerine; wherein the honey is kanuka honey
2. A honey composition as claimed in claim 1 wherein the honey is medical grade kanuka honey.
3. A honey composition as claimed in claim 1 or claim 2 which comprises about 90% w/w honey and about 10% w/w glycerine.
4. A honey composition as claimed in any one of claims 1 to 3 which has stable bio- 15 activity when stored at temperatures below room temperature.
5. A honey composition as claimed in any one of claims 1 to 3 which has stable bio- activity when stored at temperatures above room temperature. 20
6. A honey composition as claimed in any one of claims 1 to 5 which has a total activity measured against Staphylococcus aureus NZRM 87 (ATCC 9144) and expressed as equivalent % phenol, of at least about 18% phenol.
7. A honey composition as claimed in any one of claims 1 to 6 which is substantially 25 free of other components.
8. A honey composition as claimed in any one of claims 1 to 6 which comprises one or more additional components. 30
9. A method of preparing a honey composition including the step of admixing kanuka honey with glycerine, at a ratio of honey to glycerine of about 85% w/w honey : 15% w/w glycerine to about 95% w/w honey : 5% w/w glycerine.
10. A method as claimed in claim 9 wherein the honey is medical grade kanuka honey.
11. A method as claimed in claim 9 or claim 10 wherein the ratio of honey to glycerine is about 90% w/w honey : 10% w/w glycerine.
12. A method as claimed in any one of claims 9 to 11 wherein the honey composition is substantially free of other components.
13. A method as claimed in any one of claims 9 to 11 which comprises one or more 5 additional components.
14. A honey composition produced by the method of any one of claims 9 to 13.
15. A honey composition as claimed in claim 14 which has stable bio-activity when 10 stored at temperatures below room temperature.
16. A honey composition as claimed in claim 14 which has stable bio-activity when stored at temperatures above room temperature. 15
17. A honey composition as claimed in any one of claims 14 to 16 which has a total activity measured against Staphylococcus aureus NZRM 87 (ATCC 9144) and expressed as equivalent % phenol, of at least about 18% phenol.
18. A topical preparation comprising a honey composition as claimed in any one of 20 claims 1 to 8 or 14 to 17.
19. The use of an effective amount of a honey composition as claimed in any one of claims 1 to 8 or 14 to 17 in the manufacture of a medicament for treating or preventing a skin disorder.
20. The use as claimed in claim 19 wherein the skin disorder is selected from the group consisting of acne, nappy rash and rosacea.
21. The use as claimed in claim 19 wherein the skin disorder is caused by herpes simplex 30 virus 1 or 2.
22. The use as claimed in claim 20 wherein the skin disorder is rosacea.
23. A honey composition as claimed in claim 1 substantially as herein described with 35 reference to any one of Examples 1 to 3.
24. A use as claimed in claim 19 substantially as herein described with reference to Example 3.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361872799P | 2013-09-02 | 2013-09-02 | |
US61/872,799 | 2013-09-02 |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ629152A NZ629152A (en) | 2015-12-24 |
NZ629152B true NZ629152B (en) | 2016-03-30 |
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