WO2015159206A1

WO2015159206A1 - Copper alloy microparticles for use in the treatment of an external skin lesion

Info

Publication number: WO2015159206A1
Application number: PCT/IB2015/052694
Authority: WO
Inventors: James Crispian Garth Trace; Crispian Garth Newbon TRACE
Original assignee: Tracextec (Pty) Ltd.
Priority date: 2014-04-14
Filing date: 2015-04-14
Publication date: 2015-10-22

Abstract

The invention describes copper alloy microparticles for use in the treatment of an external skins lesion, and extends to describe compositions comprising copper alloy microparticles for use in the treatment of skin lesions.

Description

COPPER ALLOY MICROPARTICLES FOR USE IN THE TREATMENT OF AN

EXTERNAL SKIN LESION

FIELD OF INVENTION

This invention relates to copper alloy microparticles and/or compositions including the aforementioned, for use in treatment an external skin lesion.

BACKGROUND

Medicaments for the treatment of infection and/or inflammation and/or peculiar diseases and/or disorders and/or medical conditions are abundant, but have many disadvantages including microbial resistance. Metal containing compounds and/or compositions displaying medicinal properties are also well known, particularly in the field of inflammation and/or infection.

Although many metal containing compounds and/or compositions are known for displaying medicinal properties the same are typically slow acting and are often expensive to manufacture, and are frequently toxic. Oral drug delivery is currently the most popular choice for drug delivery since the ease, convenience, and relative lack of pain during administration results in a high level of patient compliance. As a result, the majority of pharmaceuticals today are administered in the form of tablets, capsules, powders, granules, or liquids.

Despite their popularity, conventional oral dosage forms are not necessarily the most efficacious. Some patients, particularly geriatrics and pediatrics, have difficulty ingesting solid oral dosage forms. This may be as a result of a variety of factors, ranging from the patient suffering from a condition that renders swallowing painful or difficult, to anginophobia (fear of choking) or due to the sometimes unpleasant taste. To combat this problem, alternate delivery means have been explored. The desired site of action for the drug in, or on, the human or animal in need of such drug is another important factor to bear in mind during drug design. Often, for dermatological conditions, a topical dosage form is desirable since oral dosage forms may pose several disadvantages. One such disadvantage in oral drug delivery exists in the form of the hostile environment presented by the gastro-intestinal tract (GIT) where significant quantities of the administered drug are lost due to acid hydrolysis and the hepatic 'first pass' effect. In addition, not all drugs can be incorporated into oral dosage forms due to their specific physicochemical properties.

Much research is being conducted into developing topical and transdermal drug delivery systems and also intravenous systems.

The intravenous route which provides rapid physiological relief of symptoms must only be delivered by professional personnel under medical guidance as it may lead to high drug concentrations being injected into the systemic circulation which lead to seriously detrimental consequences. The topical and transdermal routes of drug delivery offer several advantages being less invasive and can be painlessly self-administered.

Topical and/or transdermal medicaments are often easily washed and/or rubbed off the dermis where said medicaments have been applied therein decreasing their efficacy. Formulation of topical and/or transdermal medicaments often hinders the pharmaceutically active ingredient from making contact with the target site on the dermis which requires treatment. Exposure of the pharmaceutically active ingredient to ambient temperatures and atmospheric conditions may also degrade and/or oxidise said pharmaceutically active ingredient negatively impacting on the efficacy of the topical and/or transdermal medicament.

There exists a need for substances and/or compositions for use in topical and/or transdermal applications that would at least ameliorate one of the disadvantages described herein. Particularly in the case of external skin lesions there exists a need for compounds and/or compositions for use in treating such external skin lesions. External skin lesions are known to take a considerably long time period to heal and cause severe pain and discomfort to the patient. Particularly in regard to external skin lesions, there remains a need for a substance and/or composition which will facilitate external skin lesion healing, alleviate pain and discomfort, and reduce scar formation. SUMMARY

In accordance with a first aspect of the invention there is provided copper alloy microparticles for use in the treatment of an external skin lesions in a human or animal body, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιτι to about ΙΟΟμιη.

The external skin lesion may be caused by at least one of the following group: sores, cuts, grazes, burns, bruises, blisters, ulcers, warts, athlete's foot, acne, cold sores, inflammation, bed sores, infection, insect or animal bites and/or stings, shingles, early squamous cell carcinoma (Bowen's Disease), and long lasting hand sterilizer and/or deodoriser. The copper alloy microparticles may include a transition metal including, but not limited to: cobalt, nickel, silver, gold, titanium, platinum, chromium, manganese, iron and zinc. The copper alloy microparticles may include at least about 0.1% of a transition metal. Typically, the transition metal is zinc. In use the zinc may act as an antioxidant.

Typically, the copper alloy microparticles include at least about 60% copper. Applicant has surprisingly found that when the copper alloy microparticles include less than about 60% copper then the medicinal properties of the copper alloy microparticles are substantially delayed.

In an embodiment of the invention the copper alloy microparticles comprise between about 60-99% copper and between about 1-40% zinc. In another embodiment of the invention the copper alloy microparticles comprise between about 85-99% copper and about 1-15% zinc. In a preferred embodiment of the invention the copper alloy microparticles comprise about 95% copper and about 5% zinc.

In a preferred embodiment of the invention, each copper alloy microparticle has a major dimension in the range of about Ιμιτι to about 20μιη, preferably about 2μιη to about 20μιη. Typically, in use, the copper alloy microparticles are for application to an external skin lesion, for example a burn wound, on the dermis of the human or animal body in order to treat said external skin lesion. Typically, application alleviates pain and stimulates the formation of a substantially sterile scab at the site of application. The substantially sterile scab prevents infection, further reduces and/or eliminates pain, stops bleeding, and facilitates healing of the lesion and/or restoration of the dermis to a medically healthy condition, and reduces scaring. In use, contact or even near contact of the lesion with the copper alloy microparticles shows fast acting antimicrobial and/or analgesic effects.

The Applicant is unaware of prior art teaching or even suggesting copper alloy microparticles for use in the treatment of external skin lesions on the human or animal body, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη. The alleviation of pain (an analgesic effect) and the formation of the substantially sterile scab and/or the facilitated healing of the lesion was surprising and unexpected.

The copper alloy microparticles may be hydrophobic and lipophilic. The copper alloy microparticles for topical application may further be formulated into a topical composition such as a cream and/or ointment and/or powder, said composition for application to the dermis of the human or animal body. In an embodiment wherein the topical composition is a powder the powder adheres to the natural skin oils of a human or animal in use and does not readily wear off the skin. In an embodiment wherein the topical composition is a powder the powder is hydrophobic and lipophilic. The topical composition may be a hand sanitizer and/or a deodoriser.

The topical composition may further comprise an antioxidant to in use hinder oxidation of the copper alloy microparticles. Typically, the antioxidant is zinc.

In accordance with a second aspect of this invention there is provided use of copper alloy microparticles in the manufacture of a pharmaceutical composition for the treatment of external skin lesions in a human or animal body, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη.

The external skin lesion may be caused by at least one of the following group: sores, cuts, grazes, burns, bruises, blisters, ulcers, warts, athlete's foot, acne, cold sores, inflammation, bed sores, infection, insect or animal bites and/or stings, shingles, early squamous cell carcinoma (Bowen's Disease) ), and long lasting hand sterilizer and/or deodoriser.

The copper alloy microparticles may include a transition metal including, but not limited to: cobalt, nickel, silver, gold, titanium, platinum, chromium, manganese, iron and zinc. The copper alloy microparticles may include at least about 0.1% of a transition metal. Typically, the transition metal is zinc. In use the zinc may act as an antioxidant. Typically, the pharmaceutical composition includes copper alloy microparticles having at least about 60% copper. Applicant has surprisingly found that when the copper alloy microparticles include less than about 60% copper then the medicinal properties of the copper alloy microparticles are substantially delayed and/or diminished. In an embodiment of the invention the copper alloy microparticles comprise between about 60-99% copper and between about 1-40% zinc. In another embodiment of the invention the copper alloy microparticles comprise between about 85-99% copper and about 1-15% zinc. In a preferred embodiment of the invention, the pharmaceutical composition includes the copper alloy microparticles comprising about 95% copper and about 5% zinc. In a preferred embodiment of the invention, the pharmaceutical composition includes copper alloy microparticles each having a major dimension in the range of Ιμιη to about 20μιη, preferably about 2μιη to about 20μιη.

Typically, in use, the pharmaceutical composition is for application to an external skin lesion, for example a burn wound, on the dermis of the human or animal body in order to treat said external skin lesion. Typically, application alleviates pain and stimulates the formation of a substantially sterile scab at the site of application. The substantially sterile scab prevents infection, further reduces and/or eliminates pain, stops bleeding, and facilitates healing of the lesion and/or restoration of the dermis to a medically healthy condition, and reduces scaring. In use, contact or even near contact of the lesion with the copper alloy microparticles shows fast acting antimicrobial and/or analgesic effects.

The Applicant is unaware of prior art teaching or even suggesting use of copper alloy microparticles in the manufacture of a pharmaceutical composition for the treatment of external skin lesions, man or animal body, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη. The alleviation of pain (an analgesic effect) and the formation of the substantially sterile scab and/or the facilitated healing of the lesion was surprising and unexpected.

The copper alloy microparticles of the pharmaceutical composition may be hydrophobic and lipophilic. The pharmaceutical composition may further be formulated into a topical composition such as a cream and/or ointment and/or powder, said composition for application to the dermis of the human or animal body. In an embodiment wherein he topical composition is a powder the powder adheres to the natural skin oils of a human or animal in use and does not readily wear off the skin. In an embodiment wherein the topical composition is a powder the powder is hydrophobic and lipophilic.

The topical composition may be a long lasting hand sterilizer and/or deodoriser.

In accordance with a third aspect of this invention there is provided a method of treating an external skin lesion in a human or animal body comprising the steps of administering copper alloy microparticles to said human or animal body in need thereof, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη.

In accordance with a fourth aspect of this invention there is provided a pharmaceutical composition comprising copper alloy microparticles, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη, the pharmaceutical composition being for use in the treatment of external skin lesions in a human or animal body.

The external skin lesion may be caused by at least one of the following group: sores, cuts, grazes, burns, bruises, blisters, ulcers, warts, athlete's foot, acne, cold sores, inflammation, bed sores, infection, insect or animal bites and/or stings, shingles, and early squamous cell carcinoma (Bowen's Disease), and long lasting hand sterilizer and/or deodoriser. The copper alloy microparticles may include a transition metal including, but not limited to: cobalt, nickel, silver, gold, titanium, platinum, chromium, manganese, iron and zinc. The copper alloy microparticles may include at least about 0.1% of a transition metal. Typically, the transition metal is zinc. In use the zinc may act as an antioxidant.

Typically, the pharmaceutical composition includes copper alloy microparticles having at least about 60% copper. Applicant has surprisingly found that when the copper alloy microparticles include less than about 60% copper then the medicinal properties of the copper alloy microparticles are substantially delayed and/or diminished.

In an embodiment of the invention the copper alloy microparticles of the pharmaceutical composition comprise between about 60-99% copper and between about 1-40% zinc. In another embodiment of the invention the copper alloy microparticles of the pharmaceutical composition comprise between about 85-99% copper and about 1-15% zinc. In a preferred embodiment of the invention, the copper alloy microparticles of the pharmaceutical composition includes comprise about 95% copper and about 5% zinc.

In a preferred embodiment of the invention, the pharmaceutical composition includes copper alloy microparticles each having a major dimension in the range of about Ιμιη to about 20μιη, preferably about 2μιη to about 20μιη.

Typically, in use, the pharmaceutical composition is for application to an external skin lesion, for example a burn wound, on the dermis of the human or animal body in order to treat said external skin lesion. Typically, application alleviates pain and stimulates the formation of a substantially sterile scab at the site of application. The substantially sterile scab prevents infection, further reduces and/or eliminates pain, stops bleeding, and facilitates healing of the lesion and/or restoration of the dermis to a medically healthy condition, and reduces scaring.

The Applicant is unaware of prior art teaching or even suggesting use of copper alloy microparticles in the manufacture of a pharmaceutical composition for the treatment of external skin lesions in a human or animal body, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη. The alleviation of pain (an analgesic effect) and the formation of the substantially sterile scab and/or the facilitated healing of the lesion was surprising and unexpected.

The copper alloy microparticles of the pharmaceutical composition may be hydrophobic and lipophilic. The pharmaceutical composition may further be formulated into a topical composition such as a cream and/or ointment and/or powder, said composition for application to the dermis of the human or animal body. In an embodiment wherein he topical composition is a powder the powder adheres to the natural skin oils of a human or animal in use and does not readily wear off the skin. In an embodiment wherein the topical composition is a powder the powder is hydrophobic.

The topical composition may be a hand sanitizer), and long lasting hand sterilizer and/or deodoriser.

The topical composition may further comprise an antioxidant to in use hinder oxidation of the copper alloy microparticles. Typically, the antioxidant is zinc. There is provided for an embodiment of the invention, a pharmaceutical composition, to comprise elemental copper microp articles and/or elemental copper nanoparticles and a transition metal, for example zinc.

BRIEF DESCRIPTION OF THE DRAWINGS: Embodiments of the invention will be described below by way of example only and with reference to the accompanying drawings in which:

FIGURE 1 shows a second degree burn lesion in a human which is infected;

FIGURE 2 shows the lesion of Figure 1 covered in copper foil;

FIGURE 3 shows the lesion of Figure 2 after 12 hours post application of the foil; FIGURE 4 shows the lesion of Figure 2 after 24 hours post application of the foil;

FIGURE 5 shows copper alloy microparticles for use in the treatment of an external skin lesion, visibly the burn wound of Figure 1, according to a preferred embodiment of the first aspect of the invention, wherein the lesion is covered in copper alloy microparticles; FIGURE 6 shows the lesion of Figure 5 after 12 hours post application of the copper alloy microparticles;

FIGURE 7 shows the lesion of Figure 5 one week after application of the copper alloy microparticles;

FIGURE 8 shows the lesion of Figure 5 four weeks after application of the copper alloy microparticles;

FIGURE 9 shows the lesion of Figure 5 after 3 months post application of the copper alloy microparticles, the lesion being healed with substantially no scarring;

FIGURE 10 shows an external skin lesion on a dog having been cleaned but untreated;

FIGURE 11 shows a skin lesion of Figure 10 substantially covered with copper alloy microparticles; FIGURE 12 shows the skin lesion of Figure 10 one week after application of the copper alloy microparticles and shows the formation of a sterile scab and substantial healing of the skin lesion;

FIGURE 13 shows a graze external skin lesion of a human; FIGURE 14 shows the graze of Figure 13 one week after application of the copper alloy microparticles;

FIGURE 15 shows an ulcer in a human;

FIGURE 16 shows the ulcer of Figure 15 after 3 days post application of the copper alloy microparticles; FIGURE 17 shows a bedsore in a human which is infected and includes necrotic tissue; FIGURE 18 shows the bedsore of Figure 17 after being cleaned;

FIGURE 19 shows the bedsore of Figure 18 being covered in copper alloy microparticles;

FIGURE 20 shows the bedsore of Figure 19 after 1 week post application of the copper alloy microparticles; FIGURE 21 shows a bunion in a human;

FIGURE 22 shows scab formation of the bunion of Figure 21 after application of the copper alloy microparticles; and

FIGURE 23 shows the healed bunion of Figure 21 after application of the copper alloy microparticles according to the invention. DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the invention will be described below by way of non-limiting examples.

In broad terms the invention has four aspects as outlined in the Summary of the invention above. For the sake of brevity the content of the Summary is not repeated here, however, its content is fully incorporated herein by reference thereto. In accordance with a first aspect of the invention there is provided copper alloy microparticles for use in the treatment of an external skin lesion in a human or animal body, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιτι to about ΙΟΟμιη.

The external skin lesion is generally caused by at least one of the following group: sores, cuts, grazes, burns, bruises, blisters, ulcers, warts, athlete's foot, acne, cold sores, inflammation, bed sores, infection, insect or animal bites and/or stings, shingles, and early squamous cell carcinoma (Bowen's Disease), and long lasting hand sterilizer and/or deodoriser.

The copper alloy microparticles typically include a transition metal including, but not limited to: cobalt, nickel, silver, gold, titanium, platinum, chromium, manganese, iron and zinc. The copper alloy microparticles may include at least about 0.1% of a transition metal. Generally, the transition metal is zinc. In use the zinc may act as an antioxidant. The antioxidant prevents oxidation of copper. The Applicant surprising found that use of copper alloy microparticles comprising copper and another transition metal, such as zinc, provides synergistic medicinal properties when compared to the combined effect of using elemental copper and said transition metal, such as zinc, separately.

Typically, the copper alloy microparticles include at least about 60% copper. Applicant has surprisingly found that when the copper alloy microparticles include less than about 60% copper then the medicinal properties of the copper alloy microparticles are substantially diminished and/or delayed. In an embodiment of the invention the copper alloy microparticles comprise between about 60-99% copper and between about 1-40% zinc. In another embodiment of the invention the copper alloy microparticles comprise between about 85-99% copper and about 1-15% zinc. In a preferred embodiment of the invention the copper alloy microparticles comprise about 95% copper and about 5% zinc. In a preferred embodiment of the invention, each copper alloy microparticle has a major dimension in the range of about Ιμιτι to about 20μιη, preferably about 2μιη to about 20μιη.

Typically, in use, the copper alloy microparticles are for application to an external skin lesion, for example a burn wound, on the dermis of the human or animal body in order to treat said external skin lesion. Typically, application alleviates pain and stimulates the formation of a substantially sterile scab at the site of application. The substantially sterile scab prevents infection, further reduces and/or eliminates pain, stops bleeding, and facilitates healing of the lesion and/or restoration of the dermis to a medically healthy condition, and reduces scaring. In use, contact or even near contact of the lesion with the copper alloy microparticles shows fast acting antimicrobial and/or analgesic effects.

The copper alloy microparticles are typically hydrophobic and lipophilic. The copper alloy microparticles for topical application may further be formulated into a topical composition such as a cream and/or ointment and/or powder, said composition for application to the dermis of the human or animal body. In an embodiment wherein the topical composition is a powder the powder adheres to the natural skin oils of a human or animal in use and does not readily wear off the skin. In an embodiment wherein the topical composition is a powder the powder is hydrophobic and lipophilic. The hydrophobic and lipophilic nature of copper alloy microparticles and/or the powder increase the efficacy in the treatment of external skin lesions since the copper alloy microparticles and/or the powder do not readily wash and/or rub off.

The topical composition may be a long lasting hand sterilizer and/or deodoriser. The topical composition may comprise a further antioxidant to in use hinder oxidation of the copper alloy microparticles. Typically, the antioxidant is zinc. The antioxidant prevents the oxidation of the copper and has been found to increase efficacy in use.

The copper alloy microparticles are typically applied to the dermis either by human hand or through using a transferring medium such as a material cloth or ear-bud. The copper alloy microparticles may be wetted to form a paste-like composition in order to prevent the copper alloy microparticles from dislodging from their area of application.

Typically, a treatment regime includes applying the copper alloy microparticles over the area in need of treatment on the dermis, followed by re-application at least once every 24 hours for several days. The application of the copper alloy microparticles to the area in need of treatment on the dermis causes alleviation of pain and/or formation of a substantially sterile scab. The substantially sterile scab facilitates healing of the dermis to a medically healthy condition. Further pain and/or discomfort experienced by the human or animal is relieved as the dermis heals. The substantially sterile scab also prevents re-inflammation and/or re-infection of the treated dermis.

The Applicant has surprisingly found that the copper alloy microparticles provide for little or no bacterial resistance developing in use.

Swallowing of the copper alloy microparticles is to be avoided unless specifically formulated as an oral pharmaceutical dosage form. In the event of exposure of the copper alloy microparticles to human or animal eyes, wash said eyes with salad oil, repeatedly until clear then rinse out the oil with warm water.

The copper alloy microparticles, and/or the pharmaceutical compositions of the various aspects of this invention should be stored in a cool and dry place. The copper alloy microparticles have a lethal dose (LD50) in mice of >5000mg/kg that in man is unknown, and as such these doses should be avoided in use.

The application to the dermis for treatment purposes is painless since the copper alloy microparticles, and/or pharmaceutical compositions comprising the same do not cause user discomfort and is patient compliant. This was a surprising advantage found by the Applicant. The Applicant found that use of a solid piece of copper and/or copper alloy did not display the same medical properties as the invention described herein. Without being limited to theory, the Applicant proposes that the particular particle size of the copper alloy microparticles is important with respect to observed medical properties. Particularly, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη, the Applicant found such particles to be appropriate for use in the treatment and/or prevention of a disease and/or disorder and/or medical condition in a human or animal body, particularly in the treatment of external skin lesions.

The Applicant postulated that the smaller the particle size, the higher the surface area and therefore the more direct contact can be had between a site of the human or animal body being treated and the particle resulting in better treatment and/or prevention of a disease and/or disorder and/or medical condition.

The Applicant conducted tests with copper alloy microparticles and copper alloy nanoparticles, wherein each microparticle has a major dimension in the range of about Ιμιτι to about ΙΟΟμιη and, wherein each nanoparticle has a major dimension in the range of about lnm to about 999nm. Surprisingly, and unexpectedly, the Applicant has found that for the best results in use, one should use copper alloy microparticles each particle having a major dimension in the range of about Ιμιτι to about 20μιη, particularly wherein each particle having a major dimension in the range of about 2μιη to about 20μιη. It is thought that copper alloy microparticles wherein each particle has a major dimension in the range of about Ιμιτι to about ΙΟΟμιη, preferably about Ιμιτι to about 20μιη, further preferably about 2μιη to about 20μιη, are small enough to readily contact the treatment site but large enough not to pass through the dermis into the bloodstream of the human or animal undergoing treatment. Consequently, said copper alloy microparticles make contact with the treatment site for longer periods of time therein increasing efficacy in use. Although copper is non-toxic, use of copper alloy microparticles sized such that they do not pass through the dermis into the bloodstream limits the potentially dangerous side effects of excess copper being absorbed by the patient undergoing treatment. This is particularly advantageous in patients with Wilson's disease who cannot readily excrete excess copper. In a preferred embodiment the invention the copper alloy microparticles comprise copper alloy microparticles wherein each copper alloy microparticle is about 95% copper and 5% zinc.

It is envisioned that the invention may extend to copper alloy nanoparticles, elemental copper nanoparticles and elemental copper microparticles for use in the treatment of an external skin lesion, wherein each microparticle has a major dimension in the range of about Ιμιτι to about ΙΟΟμιτι and, wherein each nanoparticle has a major dimension in the range of about lnm to about 999nm.

It is further envisioned that the invention may extend to copper alloy nanoparticles for use in the treatment of infection, wherein the copper alloy nanoparticles are formulated as an injectable preparation for injection into a human or animal body in need thereof. Typically, when the copper alloy nanoparticles are formulated as an injectable preparation, the copper alloy nanoparticles are formulated together with a surfactant. The surfactant may include, but is not limited to, naturally occurring nontoxic agents. Typically, the surfactant is isotonic, more preferably the surfactant is coconut milk. The injectable preparation may be for intravenous application.

The invention may extend to include certain dosing regimes which may include copper alloy microparticles and/or copper alloy nanoparticles, wherein the copper alloy microparticles and/or copper alloy nanoparticles are for administration to the human or animal body in a certain amount at predetermined time intervals, wherein each copper alloy microparticle has a major dimension in the range of about Ιμιη to about ΙΟΟμιη and, wherein each copper alloy nanoparticle has a major dimension in the range of about lnm to about 999nm.

It is envisioned that elemental copper microparticles and/or elemental copper nanoparticles may be used in the treatment of a human or animal body to treat disease, typically infection. Said elemental copper microparticles and/or elemental copper nanoparticles may be formulated together with a transition metal into a pharmaceutical composition. Said pharmaceutical composition may include zinc as the transition metal. Zinc may in use act as an antioxidant. The pharmaceutical composition may be formulated as a power, ointment, cream, or as an injectable preparation. The pharmaceutical composition may comprise about 95% elemental copper microparticles and/or elemental copper nanoparticles and about 5% zinc.

It is envisioned that elemental copper microparticles, elemental copper nanoparticles, copper alloy microparticles and copper alloy nanoparticles may be used as anti-toxin agents which may, for example, be used in the treatment of bee stings, spider bites and scorpion stings. The Applicant was surprised to find anti-toxic properties of the aforementioned particles. EXAMPLES:

Comparative Example 1

Copper foil was used on a second-degree steam burn located on the forearm of an elderly man. A thin 25μιη copper foil piece was taped onto the raw, but well washed, surface of the lesion. The lesion was oval, approximately 30mm x 40mm and had, over the course of three days since the injury, become infected, inflamed and very painful. The lesion was wiped, to remove excessive pus, using soap and water with a soft tissue. The foil was painlessly taped directly onto the lesion. The foil was left on the lesion for a total of 24hrs. Figure 1 shows a second degree burn lesion which has become infected. Figure 2 shows the lesion of Figure 1 having been covered with the copper foil. Figure 3 shows the lesion of Figure 2 at 12 hours after application of the copper foil indicating that the copper foil is not successful in treating the lesion. Figure 4 shows the lesion of Figure 3 at 24 hours after application of the copper foil indicating that the copper foil is not successful in treating the lesion. No healing or pain relief resulted from the foil treatment. The lesion remained very painful and became moist from being covered. The infection continued.

Example 2:

In a first example of the invention there is provided copper alloy microparticles, for use in the treatment of an external skin lesion on a human, the skin lesion being a burn wound, each particle having a major dimension in the range of about Ιμιη to about 20μιη. The copper alloy microparticles comprise 95% copper and 5% zinc. Zinc in use acts as an antioxidant. The Applicant surprising found that use of copper alloy microparticles comprising copper and another transition metal, such as zinc, provides synergistic medicinal properties when compared to the combined effect of using elemental copper and said transition metal, such as zinc, separately.

The copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties, was used on a second-degree steam burn, on the forearm of an elderly man. A covering of this powder was spread onto the raw, but well washed, surface of the lesion. The lesion was oval, approximately 30mm x 40mm and had, over the course of five days since the injury, become infected, inflamed and very painful. Within minutes of applying the treatment, the patient reported that he could feel the pain subsiding, and that the pain had gone completely within an hour.

The lesion was wiped, to remove excessive pus, using soap and water with a soft tissue. The powder was painlessly applied directly from the bottle onto the lesion. A layer was created, covering the entire surface of the lesion, as well as some of the surrounding skin. A scab incorporating the powder was encouraged to form, and this was allowed to dry. Only where the scab cracked was additional powder applied after a few days. When needed, additional powder was applied, especially where the scab cracked. Normal bathing and movement continued throughout the treatment of the arm. Healing was rapid and pain was controlled by the full contact of the powder on the lesion and in the scab. New skin appeared from around the edges as a silky- smooth pink layer could be seen growing in under the scab 6 to 10 days after the powder was applied the scab fell off leaving a healed, blemish-free lesion. Subsequently, the skin returned to the normal colour of the surrounding skin, without further incident, and there has been no disfigurement, scarring or cicatricle contraction.

Figure 5 shows copper alloy microparticles for use in the treatment of the burn lesion of Figure 1 according to a preferred embodiment of the first aspect of the invention, wherein the copper alloy microparticles have been applied to the lesion. Figure 6 shows the lesion of Figure 5, 12 hours after application of the copper alloy microparticles and it is evident that the wound is undergoing healing. Figure 7 shows the lesion of Figure 5, one week after application of the copper alloy microparticles. Figure 8 shows the lesion of Figure 5 four weeks after application of the copper alloy microparticles. Figure 9 shows the lesion 3 months after application of the copper alloy microparticles, the lesion being healed with substantially no scarring. It can be seen that the copper alloy microparticles facilitates healing of the lesion as time passes. The patient provided feedback that application of the copper alloy microparticles provided near immediate pain relief. The copper alloy microparticles used in this Example 2 were in powder form.

The powder was hydrophobic and lipophilic owing to the hydrophobic and lipophilic nature of the copper alloy microparticles. The hydrophobic and lipophilic nature of the powder prevented it from being washed and/or rubbed off the patient. The same powder that was used in this Example 2 was used in the Examples 3 to 18 below.

Example 3:

In a third example of the invention there is provided copper alloy microparticles, for use in the treatment of an external skin lesion on an animal, the skin lesion being a burn wound, each particle having a major dimension in the range of about Ιμιη to about 20μιη. The copper alloy microparticles comprise 95% copper and 5% zinc. Zinc in use acts as an antioxidant. The Applicant surprising found that use of copper alloy microparticles comprising copper and another transition metal, such as zinc, provides synergistic medicinal properties when compared to the combined effect of using elemental copper and said transition metal, such as zinc, separately. Figure 10 shows an external skin lesion on a dog having been cleaned but untreated. Figure 11 shows the skin lesion of Figure 10 substantially covered with copper alloy microparticles as described above. Figure 12 shows the skin lesion of Figure 10 one week after application of the copper alloy microparticles and shows the formation of a sterile scab and substantial healing of the skin lesion. The Applicant noticed rapid epithelisation and healing of the skin lesion. No antibiotics were administered to assist with healing. The dog displayed reduced signs of pain after the application of the copper alloy microparticles to the lesion. The copper alloy microparticles used in this Example 3 were in powder form.

The powder was hydrophobic and lipophilic owing to the hydrophobic and lipophilic nature of the copper alloy microparticles. The hydrophobic and lipophilic nature of the powder prevented it from being washed and/or rubbed off the patient.

Example 4:

In a fourth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a severe graze on the shin of a man. The man was in great pain. A covering of this powder was placed onto the raw, but well washed, surface of the lesion. The lesion was approximately 200mm long and 10mm wide, and was likely to be infected, as a dirty, rusty old wooden bridge had caused it. Within a minute of applying the treatment, the patient reported that the pain had subsided to 10% of the initial pain felt.

The lesion was washed with water, to remove excessive dirt, using his hand. The powder was painlessly applied directly from the bottle onto the lesion. A layer was spread, covering the entire surface of the lesion, as well as some of the surrounding area. A scab incorporating the powder was encouraged to form, and this was allowed to dry without any covering. Healing was painless and was controlled by the full contact of the powder on the lesion and in the scab. The man reported slight tingling feeling after the treatment and very little pain. Figures 13 shows the lesion covered with the copper alloy microparticles and Figure 14 shows the lesion 1 week after the application of the copper alloy microparticles. New skin appeared, around and under the scab, which fell off completely after about 7 days. Some areas took longer to heal due to the depth of the wound. The result is now blemish free. Example 5:

In a fifth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a chronic ulcer, on the shin of an elderly woman. A covering of this powder was spread onto the raw, but well cleaned, surface and into the depth of the lesion. The lesion was rectangular approximately 10 by 20mm in length, and had, over the course of three months since the injury, become infected, inflamed and painful. The lesion was wiped clean, using a soft tissue. The powder was applied directly from the bottle onto the lesion. A layer of powder was created, covering the entire surface and depth of the lesion, as well as some of the surrounding skin. A scab incorporating the powder was encouraged to form, and this was allowed to dry without any covering. Healing was rapidly controlled by the full contact of the powder on the lesion and in the scab. New skin appeared from around the edges as a silky- smooth pink layer and could be seen growing in under the scab. The woman was very happy with the rapid results and pain relief. She had tried many other treatments without any success. Figure 15 shows the ulcer and Figure 16 shows the ulcer 3 days after application of the copper alloy microparticles powder. Example 6:

In a sixth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a chronic bedsore, on the shoulder of an elderly woman. A covering of the powder was spread onto the raw, but well cleaned, surface and worked into the depth of the lesion. The lesion was oval approximately 25 to 50mm in diameters, and had, over the course of four months since the injury, become infected, inflamed and very smelly. The patient has been getting treatment from a hospital up until application of the powder. The woman is a paraplegic with only a little feeling in her shoulder, as a result has little pain.

The lesion was wiped with Hydrogen peroxide, to clean and remove the pus, all necrotic tissue was removed with forceps. The lesion was again thoroughly cleaned with hydrogen peroxide. The peroxide was then fully removed. The powder was applied directly from the bottle onto the lesion. A layer was created, covering the entire surface and depth of the lesion, as well as some of the surrounding skin. A scab incorporating the powder was encouraged to form, and this was allowed to dry without any covering. Additional powder was applied daily, and additional cleaning when needed. Healing was rapid and controlled by the full contact of the powder on the lesion and in the scab. After one week new flesh appeared to be growing from the depth of the wound, as well as a silky- smooth layer of pink, new skin growing in from the edges under the scab. Figure 17 shows the bedsore prior to cleaning clearly showing the bedsore is infected with necrotic tissue. Figure 18 shows the cleaned bedsore. Figure 19 shows the cleaned bedsore after application of the powder, and Figure 20 shows the bedsore 1 week after application of the powder.

Example 7:

In a seventh example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a chronic fungal infection, on the foot and toes of a man. A covering of this powder was spread onto the raw, but well washed, surface of the lesion. The infection covered most of the toes and front area of the foot, and had, over the course of two months, become infected, inflamed and very painful. The man could hardly walk. Within minutes of applying the treatment, the patient reported that he could feel the pain subsiding, and that the pain had gone completely within a few hours.

The fungal infection was wiped, to remove excessive loose skin, using a soft tissue. The powder was painlessly applied directly from the bottle onto the lesion. A layer was created, covering the entire surface of the lesion, as well as some of the surrounding skin. A scab incorporating the powder was encouraged to form, and this was allowed to dry whenever possible without any covering. Additional powder applied daily for the first week, after which, only when required. Normal bathing and movement continued throughout the treatment of the foot. The man was able to walk to and from work. Healing was rapid and pain was controlled by the full contact of the powder on the fungal infection and in the scabs where it formed. New skin appeared. After 6 to 10 days the scabs fell off leaving a healed, blemish-free lesion. Subsequently, the skin returned to the normal colour of the surrounding skin, without further incident. Example 8:

In an eighth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a severe bunion on the foot of an elderly woman. The bunion had been present for more than a year and the woman was in considerable pain and discomfort. A covering of this powder was placed onto the raw, but well washed, surface of the lesion. The bunion was approximately 15mm in diameter, and was not healing despite the many different treatments that had been tried by doctors and hospitals. Within minutes of applying the treatment, the patient reported that the pain had subsided substantially. Figure 21 shows a bunion prior to application of the powder. Figure 22 shows scab formation after application of the powder, and Figure 23 shows healing of the bunion after application of the powder.

The powder was painlessly applied directly from the bottle onto the lesion. A layer was spread, covering the entire surface of the lesion, as well as some of the surrounding area. The patent was asked to leave the lesion uncovered, and not to wear shoes or socks. A scab incorporating the powder was encouraged to form, and this was allowed to dry without any covering. Healing was painless and was controlled by the full contact of the powder on the lesion and in the scab. The woman reported no more pain after the initial treatment and was able to walk normally within ten days.

Example 9:

In a ninth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a severe case of acne symptoms on the face of a young girl. After careful cleaning, a covering of this powder was placed all over the face where the acne was prevalent. Special care was taken to cover all open acne sores.

The powder was painlessly applied onto the infected area with a soft brush. A very thin layer was spread over the entire infected area, as well as some of the surrounding area. Special care was taken to cover all open pimples and heads. A daily light treatment was used in the morning and a heavier treatment just before bedtime. The light treatments continued after the acne had cleared up to prevent any re-occurrence.

Healing was quick and was controlled by the full contact of the powder on the acne and the surrounding areas. The family were all very happy with the treatment.

Example 10:

In a tenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a painful cold sore on the lip of a woman. A covering of the powder was put onto the cold sore regularly.

The powder was painlessly applied directly from the bottle onto the cold sore, covering the entire area. A daily light treatment was used in the morning and a heavier treatment just before bedtime. Healing was quick and was controlled by the full contact of the powder on the cold sore. The woman was very happy with the quick pain relief and fast healing.

Example 11;

In an eleventh example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a bad case of shingles covering the legs of a woman. A covering of this powder was placed over the legs where the painful shingles rash was prevalent. The woman was delighted with the results saying it was the first good night's sleep without pain in months.

The powder was applied to a soft make-up brush and from there painlessly onto the rash. A layer was spread over the entire infected area, as well as some of the surrounding area. A nightly treatment was used just before bedtime, and again in the mornings, until the rash had subsided. Healing was quick and was controlled by the full contact of the powder on the shingles and the surrounding areas. The woman was very happy with the results that alleviated the pain and distress of the shingles rash. Example 12:

In a twelfth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on warts, on the hands of a woman. A covering of this powder was well worked onto and into the surface of the warts. The warts disappeared after 5 days treatment.

The powder was applied directly from the bottle onto the warts. The treatment was applied two to three times a day and well rubbed onto and into the warts each time. Treatment continued for 10 days until all evidence of the warts were gone and the skin had healed completely. Healing was controlled by the full contact of the powder on the warts and the surrounding areas. The woman was very happy with the results.

To accelerate the process the warts can be scarified and the powder then applied. Example 13:

In a thirteenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on itchy mosquito bites, on the legs of a man. A covering of this powder was placed all over the bites and surrounding swelled area. The itchy feeling from the bites disappeared within minutes and never returned.

The powder was applied directly from the bottle onto the bites, as well as the surrounding area. The treatment was applied only once. Healing was controlled by the full contact of the powder on the bites and the surrounding areas. The man was very happy with the results, as the powder removed the uncomfortable itch.

Example 14: In a fourteenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on extremely nasty midge bites, on the legs and ankles of a man. A covering of this powder was placed all over the bites and surrounding swollen and infected area. The itchy feeling from the bites disappeared within minutes, but had to be used for several days before the bites subsided completely

The powder was applied directly from the bottle onto the bites, as well as the surrounding area. The treatment was applied whenever the itching started up again. Healing was controlled by the full contact of the powder on the bites and the surrounding areas. The man was very happy with the results, as the powder removed the uncomfortable itch.

Example 15:

In a fifteenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on a very painful bee sting on the lip of a woman. A covering of this powder was placed on the sting hole and surrounding swollen area. Special attention was given to rubbing the powder into the bee sting hole. The pain from the bite disappeared within minutes, and the swelling reduced fast.

After removal of the sting, the powder was applied directly from the bottle onto the site, as well as the surrounding area. Additional powder was rubbed into the hole left by the sting. The treatment was applied only once. Healing was controlled by the full contact of the powder on the bite and the surrounding areas. The woman reported that the pain was gone within a minute. The swelling on the lip had totally disappeared after 30 minutes. The woman was very impressed with the result and had forgotten the incident had happened. Example 16:

In a sixteenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on painful scorpion bite on the foot of a boy. A covering of this powder was placed all over the site and surrounding swollen area. The pain from the sting disappeared within minutes and never returned.

The powder was applied directly from the bottle onto the site, as well as the surrounding area. Additional powder was rubbed into the hole left by the sting. The treatment was applied only once. Healing was controlled by the full contact of the powder on the bite and the surrounding areas. The boy was very happy with the results, as the powder removed the incredible pain fast. Example 17:

In a seventeenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used on painful spider bite lesion on the leg of a man. A few days after the bite, a covering of this powder was placed all over the bite and surrounding swelled area. The pain from the bite disappeared within hours and never returned.

The powder was applied directly from the bottle onto the bite lesion, as well as the surrounding area. The treatment was reapplied for 4 days, or whenever the powder was washed off. Healing was controlled by the full contact of the powder on the bite and the surrounding areas. The powder removed the incredible pain first. The treatment continued until the surrounding infected skin healed. The man was very happy with the results.

Example 18:

In an eighteenth example of the invention there is provided copper alloy microparticles being a micro-fine metallic dry powder of a copper-rich alloy with analgesic and antimicrobial properties used was tested as a hand steriliser. The hands of a man were contaminated with mixture of four common bacteria. A light covering of this powder was placed on the fingertips and rubbed all over the hands. Swabs were taken after only 5 minutes and found to have zero bacteria. The powder remains on the hands for 4 to 6 hours. This makes the steriliser long lasting and active while the powder is present on the hands.

A mixture of four common disease-causing bacteria were mixed and rubbed onto the hands and allowed to dry. A swab was taken from the palm of the contaminated hand. The powder was applied to the fingertips and then rubbed all over the hands. Five minutes later, another swab was taken from the palm of the other hand. A control swab was also taken. The test was done in the controlled environment of the laboratory. The swabs were cultured and the report was issued. The contaminated hand swab showed high levels of each bacterium: Staphylococcus aureus #240 cfu, E. coli #750 cfu , Coliforms #750 cfu, P. aeruginosa #120 cfu (estimated). The sterilising powder after 5 minutes swab showed NO GROWTH on all four bacterium. The control buffer swab had less than one cfu.

While the invention has been described in detail with respect to specific embodiments thereof, it will be appreciated that those skilled in the art, upon attaining an understanding of the foregoing may readily conceive of alterations to, variations of and equivalents to these embodiments. Accordingly, the scope of the present invention should be assessed as that of the claims and any equivalents thereto that are appended hereto.

Claims

CLAIMS:

1. Copper alloy microparticles for use in the treatment of an external skin lesion in a human or animal body, wherein each copper alloy microparticle has a major dimension in the range of Ιμιη to ΙΟΟμιη.

2. The copper alloy microparticles according to claim 2, wherein the external skin lesion is caused by at least one of the following group: sores, cuts, grazes, burns, bruises, blisters, ulcers, warts, athlete's foot, acne, cold sores, bed sores, inflammation, infection, insect or animal bites and/or stings, shingles, early squamous cell carcinoma (Bowen's Disease), hand sterilizer and deodoriser.

3. The copper alloy microparticles according to claim 2, wherein the skin lesion is a burn, and topical application of said copper alloy microparticles to said burn alleviates pain and stimulates the formation of a substantially sterile scab which scab prevents infection, further reduces and/or eliminates pain, stops bleeding, facilitates healing of the lesion and/or restoration of the dermis to a medically healthy condition, and reduces scaring.

4. The copper alloy microparticles according to any one of claims 1-3, wherein the copper alloy microparticles are formulated into a topical composition, preferably a cream and/or ointment and/or a powder, said composition being for application to the dermis of the human or animal body.

5. The copper alloy microparticles according to any one of claims 1-4, wherein the copper alloy microparticles comprise between 60-99% copper and between 1-40% zinc.

6. The copper alloy microparticles according to any one of claims 1-4, wherein the copper alloy microparticles comprise between 85-99% copper and 1-15% zinc.

7. The copper alloy microparticles according to any one of claims 1-4, wherein the copper alloy microparticles comprise 95% copper and 5% zinc.

8. The copper alloy microparticles according to any one of claims 1-8, wherein each copper alloy microparticle has a major dimension in the range of Ιμιη to 20μιη.

9. A pharmaceutical composition comprising copper alloy microparticles, wherein each copper alloy microparticle has a major dimension in the range of Ιμιη to ΙΟΟμιη.

10. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is formulated into a topical composition, preferably a cream and/or ointment and/or a powder, said composition being for application to the dermis of the human or animal body.

11. The pharmaceutical composition according to claim 9 or 10, wherein the copper alloy microparticles comprise between 60-99% copper and between 1-40% zinc.

12. The pharmaceutical composition according to claim 9 or 10, wherein the copper alloy microparticles comprise between 85-99% copper and 1-15% zinc.

13. The pharmaceutical composition according to claim 9 or 10, wherein the copper alloy microparticles comprise 95% copper and 5% zinc.

14. The pharmaceutical composition to any one of claims 9-13, wherein each copper alloy microparticle has a major dimension in the range of Ιμιη to 20μιη.