Gold Particle for Use in Therapy to Prevent Scar Formation

Abstract

A gold particle having at least one cross-section in the range of 20-1000 μnm and having a purity greater than 99.00% w/w, preferably 99.99% w/w for use in treatment of a wound to minimize scar formation and to prevent abnormal scar formation. A composition comprising at least one gold particle having at least one cross-section in the range of 20-1000 μm and having a purity greater than 99.00% w/w, preferably 99.99% w/w for use in treatment of a wound to prevent abnormal scar formation, wherein the composition further comprises hyaluronic acid or any other physiologically acceptable carrier.

Claims

1. A method of treatment comprising administering gold particle having a cross-section in the range of 20-1000 μm and having a purity greater than 99.00% w/w, preferably 99.99% w/w to a patient to prevent or reduce the formation of a scar during healing of a wound.

2. The method of claim 1, wherein the gold particle is administered prophylactically therapy to prevent or reduce the formation of a scar during healing of a wound.

3. The method of claim 1, wherein the cross-section of the gold particle is in the range of 20-40 microns

4. The method of claim 1, wherein the gold particle is formed as a micron ball gold thread.

5. The method of claim 1, wherein an effective amount of the gold particle is administered into the wound accessible for contact with immune cells of a patient.

6. The method of claim 1, wherein the scar is formed from granulation tissue.

7. The method of claim 1, wherein the scar is a keloid, a hypertrophic or an atrophic scar.

8. The method of claim 1, wherein the wound is a chronic wound or a diabetic wound.

9. The method of claim 1, wherein the therapy reduces pain in patients susceptible to abnormal scarring.

10. The method of claim 1, wherein the scar is a sub epithelial scar resulting from use of local bone restoration, or paradentosis.

11. The method of claim 1, wherein the wound is a psoriasis wound.

12. The method of claim 10, wherein the local bone restoration is a filling.

13. The method of claim 1, wherein the method comprises administering the gold particle to a patient in need thereof.

14. A composition comprising at least one gold particle having a cross-section in the range of 20-1000 μm and having a purity greater than 99.00% w/w, preferably 99.99% w/w and optionally any other physiologically acceptable carrier for use in therapy to prevent or reduce the formation of a scar during healing of a wound.

15. The composition according to claim 14, wherein the physiologically acceptable carrier is hyaluronic acid.

16. A method of treatment of a wound of an animal or human patient to prevent scar formation, wherein an effective amount of gold particles having a cross-section in the range of 20-1000 μm and having a purity greater than 99.00% w/w, preferably 99.99% w/w is applied into the wound and made accessible for contact with immune cells of the patient, thereby said gold particles are facilitated to release free gold ions by dissolucytosis.

17. The method of claim 16, wherein said gold particles are applied directly into the base of the wound and/or administered by injection into the affected tissue of the wound.

18. The method of claim 16, wherein the wound originates from a surgical incision, the method comprising the steps of applying to the exposed tissue of the surgical incision an effective amount of a composition comprising gold particles having a cross-section in the range of 20-1000 μm or any other physiologically acceptable carrier, the composition is administered along said walls of the incision and into said walls.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0047] The skilled artisan will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.

[0048] FIGS. 1a and b show X-ray photographs of a patient with an implant just after implantation and after 8 months

DETAILED DESCRIPTION OF THE INVENTION

[0049] Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.

[0050] All patents and publications referred to herein are expressly incorporated by reference.

[0051] Numeric ranges are inclusive of the numbers defining the range.

[0052] The headings provided herein are not limitations of the various aspects or embodiments of the invention. Accordingly, the terms defined immediately below are more fully defined by reference to the specification as a whole.

[0053] When used herein, the term gold or gold particle is to be understood as metallic gold, not a solute such as gold ions in a medium.

[0054] When used herein, the term gold or gold particle is used interchangeable with gold implant.

[0055] When used herein, the terms “wound”, “ulcer”, “lesion” or “trauma” is to be understood as an injury to the subject, which has left the injured tissue or organ discontinued, such as an injury of the skin and underlying tissues, by a cut, rip, incision etc. It is contemplated that these terms may cover other kinds of injuries requiring healing or restoration of tissue.

[0056] When used herein, the term granulation tissue is to be understood as new connective tissue and tiny blood vessels that form in relation to wound healing.

[0057] When used herein, the term keloid or keloidal scar is to be understood as formation of an abnormal type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation tissue (collagen type III) at the site of a healed skin injury which is then slowly replaced by collagen type I. Keloids are firm, rubbery lesions or shiny, fibrous nodules, and can vary from pink to the color of the patient's flesh or red to dark brown in color. A keloid scar is benign and not contagious, but sometimes accompanied by severe itchiness, pain, and changes in texture.

[0058] When used herein, the term hypertrophic scar is to be understood as formation of an abnormal type of scar which is a cutaneous condition characterized by deposits of excessive amounts of collagen which gives rise to a raised scar, but not to the degree observed with keloids. Like keloids, they form most often at the sites of pimples, body piercings, cuts and burns. They often contain nerves and blood vessels. They generally develop after thermal or traumatic injury that involves the deep layers of the dermis. When a normal wound heals, the body produces new collagen fibers at a rate which balances the breakdown of old collagen. Abnormal scars such as hypertrophic scars are red and thick and may be itchy or painful.

[0059] When used herein, the term an atrophic scar is to be understood as formation of an abnormal type of scar which is a sunken recess in the skin, which has a pitted appearance. These are caused when underlying structures supporting the skin, such as fat or muscle, are lost. This type of scarring is often associated with acne, chickenpox, other diseases, especially Staphylococcus or MRSA infection, surgery, or accidents.

[0060] When used herein, the term chronic wound is to be understood as a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic. Chronic wounds seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long. In acute wounds, there is a precise balance between production and degradation of molecules such as collagen; in chronic wounds this balance is lost and the healing is impaired.

[0061] When used herein, the term ‘gold thread micron ball’ is a thread of pure gold rolled into a micron-sized ball. The gold tread may have any diameter, preferably 50 micron to ensure a large surface to gold ratio. The gold thread micron ball may be placed directly into the wound as a micro implant.

[0062] Gold particles according to the invention may be dispersed in a carrier substance at a concentration of at least 0.1 mg/ml of gold particles, preferred 1 mg/ml, more preferred 5 mg/ml and most preferred 10 mg/ml of gold particles. The amount of gold in a carrier substance very with the size of the wound. Often 2 ml of gold in a carrier substance such as hyaluronic acid with a concentration of 10 mg/ml of gold is sufficient to cover the lining of a wound. In one embodiment 10 mg/ml of gold corresponds to approximately 72.000 gold particles per ml.

[0063] Treatment may be initiated at any time during the healing of a wound, however, the greatest effect of preventing or reducing scarring is when the gold is applied into the wound as soon as possible and at least before suture. One dose treatment is sufficient since the gold will remain for a lifetime in the tissue of the patient where it has been placed.

[0064] In order to further illustrate the present invention, the following specific examples are given with the understanding that they are being offered to illustrate the present invention and should not be construed in any way as limiting its scope.

Background Example

[0065] Gold particles usable in the invention implanted into injured brain tissue of mice revealed that the dissolucytotic gold ions suppress inflammation and influence the healing process in several different ways. 20-45 μm gold particles were injected into the neocortex of mice before generating a cryo-injury. It was found that the released gold ions reduced microgliosis and neuronal apoptosis, inflicted a transient astrogliosis, and increased the neural stem cell (NSC) response (Larsen A, Kolind K, Pedersen D S, Doering P, Pedersen M O, Danscher G, et al. (2008), “Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury”, Histochem. Cell Biol. 130(4), 681-92). Following unilateral treatment with gold particles, NSC stimulation with increased M-CSF expression was seen. The metallic gold treatment also significantly increased the expression of the growth factors VEGF, FGF, LIF and neurotrophin-4 (Pedersen M Ø, Larsen A, Pedersen D S, Stoltenberg M, Penkova M (2009), “Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury”, Histol. Histopathol. 24(5):573-86; Pedersen M Ø, Larsen A, Stoltenberg M, Penkowa M (2010), “Bio-released gold ions modulate expression of neuroprotective and hematopoietic factors after brain injury”, Brain Res. 1307, 1-13). Furthermore, metallic gold has been found to reduce TNF-α expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury, while at the same time an increase in the expression of the neuroprotective proteins MTI was recorded (Pedersen M O, Larsen A, Pedersen D S, Stoltenberg M, Penkowa M (2009), “Metallic gold reduces TNFalpha expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury”, Brain Res. 19, 1271-103-13).

[0066] The neuroprotective and regeneratory qualities of metallic gold were seen as a reduction of apoptotic cell death at both the early and the late phase, and NSE and TUNEL staining confirmed a gold dependant circumvention of apoptosis in neurons (Larsen et al. 2008).

[0067] The amount of gold injected into the neocortex of the mice was 5.4 mg pure gold while the amount of bio-released gold ions was so low that only the most sensitive quantitative analyses can trace such small amounts. The tool that has made it possible to observe the dissolucytotic activities leading to liberation of gold ions is the histochemical technique autometallography (AMG) (Danscher G (1981) “Localization of gold in biological tissue: A photochemical method for light and electron microscopy”, Histochemistry 71, 81-88; Danscher G, Stoltenberg M (2006), “Autometallography (AMG): Silver enhancement of quantum dots resulting from (1) metabolism of toxic metals in animals and humans, (2) in vivo, in vitro and immersion created zinc-sulphur/zinc-selenium nanocrystals, (3) metal ions liberated from metal implants and particles”, Prog. Histochem. Cytochem. 41, 57-139).

[0068] In conclusion, bio-liberated gold ions have been shown to possess pronounced anti-inflammatory, neuroprotective and neurostimulatory capacities in the mouse brain and as inflammation in the central nervous system (CNS) has been found to resemble the inflammatory processes taking place in other tissues.

Example of the Invention

[0069] In another example according to the invention a patient having a dental implant was treated for paradentosis by the insertion of gold implants, made up of a ball of a 50 micron thick wire of 99.99% pure gold, having a cross-section of 1000 μm. The gold implants/particles were injected into the periodontium in proximity to the gold implant as shown in FIG. 1A. FIG. 1B shows the position of the gold particles after 8 months. Neither the gold implants nor the dental implants had moved position in the period of time. A visible regrowth of bone had taken place.

[0070] Further embodiments of the invention are:

Embodiment 1

[0071] Method of treatment of a wound of an animal or human patient to prevent scar formation, wherein an effective amount of gold particles having a cross-section in the range of 20 - 1000 pm and having a purity greater than 99.00% w/w, preferably 99.99% w/w is applied into the wound and made accessible for contact with immune cells of the patient, thereby said gold particles are facilitated to release free gold ions by dissolucytosis.

Embodiment 2

[0072] Method of treatment according to embodiment 1, wherein said gold particles are applied directly into the base of the wound and/or administered by injection into the affected tissue of the wound.

Embodiment 3

[0073] Method of treatment according to embodiments 1 or 2, wherein the wound originates from a surgical incision, the method comprising the steps of applying to the exposed tissue of the surgical incision an effective amount of a composition comprising gold particles having a cross-section in the range of 20-1000 μm or any other physiologically acceptable carrier, the composition is administered along said walls of the incision and into said walls.

Embodiment 4

[0074] Use of at least one gold particle having a cross-section in the range of 20-1000 μm and having a purity greater than 99.00% w/w, preferably 99.99% w/w for the cosmetic treatment of scar formation during healing of a wound.

Embodiment 5

[0075] Use of at least one gold particle according to embodiment 4 in fillers for cosmetic treatment of sub epithelial scar formation.