GB2624421A

GB2624421A - Scar tissue prophylaxis

Info

Publication number: GB2624421A
Application number: GB2217192.0A
Authority: GB
Inventors: Dakin Myles; Aspinall Richard; Kenny Thomas; Chapman Christopher
Original assignee: Hypo Stream Ltd
Current assignee: Hypo Stream Ltd
Priority date: 2022-11-17
Filing date: 2022-11-17
Publication date: 2024-05-22
Also published as: WO2024105186A1; GB202217192D0

Abstract

A 0.01-0.2 wt.% hypochlorite solution for use in the prevention or treatment of scar tissue in a mammal. A pharmaceutical composition for use in the prophylactic treatment of scar tissue comprising the hypochlorite solution, a cosmetic method for improving the appearance of scar tissue comprising administering the hypochlorite solution topically and a 0.01-0.2% hypochlorite solution for use in the treatment of purpura fulminans are also included. The scar tissue may be keloid or hypertrophic scar tissue or scar contractures. The composition may be used to treat conditions characterised by abnormal production of collagen (collagen diseases), such as lung scarring caused by pulmonary fibrosis, chronic obstructive pulmonary disease (COPD) and long COVID-19. The composition may be administered to the lungs via inhalation. The hypochlorite may be sodium hypochlorite. The solution may be aqueous and comprise 0.01-0.1% hypochlorite and 0.2-3% sodium chloride. The composition may be pH 5-11 and may be unbuffered. The treatment of scar tissue may be the treatment of purpura fulminans. The composition may be applied topically, preferably to a wound such as a sutured or open wound which may be in the period of healing such as less than 10 days old.

Description

SCAR TISSUE PROPHYLAXIS

FIELD OF THE INVENTION

The present invention relates to a hypochlorite solution for the prophylactic treatment of, or treatment of, scar tissue in a mammal.

BACKGROUND

Scar tissue is a fibrous tissue that forms following trauma to the skin as part of the healing process, or as a result of particular diseases or conditions. Scar tissue is typically formed of collagen and has several differences compared to normal healthy tissue. For instance, scar tissue on the surface of the skin may be characterised by one or more of a raised profile, discoloration, increased sensitivity to sunlight, tightness/reduced elasticity, an absence of sweat glands, and an absence of hair follicles, as compared to normal skin tissue surrounding the scar. Scar tissue may also form internally within the body following major trauma (e.g. internal scars following surgery).

Scar tissue is typically less flexible than normal tissue because the collagen proteins formed during the healing process typically form in a unidirectional manner. This LtD 20 causes a reduction in tissue elasticity, which may result in recurring pain for a patient and/or restrictions to their normal range of motion. From a cosmetic point of view, scar tissue on the surface of the skin is generally considered to be unsightly.

Whilst the formation of scar tissue is a familiar part of the healing process, there is nevertheless a need to mitigate the effects of scar tissue. Wounds to the skin are generally sutured following trauma in an attempt to realign the skin in its natural position insofar as possible, to reduce or mitigate the size of the scar. Where there has been a skin graft, this may not be possible and so scarring is more extensive.

According to NHS England, the majority of treatments available for scar tissue are directed to improving the appearance of a scar that has already formed, or is in the latter stages of healing. For instance, make-up, steroids, laser therapy, cryotherapy, dermal fillers, skin needling, surgery and topical creams are used to improve the appearance of a scar. With regards to topical application, creams and oils such as BioOil® are used to improve the appearance scars and stretch marks that have already formed. Such creams and oils are not suitable for application to an open wound at an early stage of the healing process. Treatments for flattening and softening scars includes silicone gels and pressure dressings. However, again, neither of these treatments can be applied to open wounds, and pressure dressings require specialist supervision (e.g. for large scars after skin grafts).

In summary, the current standard of care is to treat scar tissue that has already formed. Existing treatments are not suitable for treating open wounds or wounds early in the stage of the healing process, with a view to mitigating or reducing the formation of scar tissue in the first instance. There are limited treatments available for reducing or mitigating the formation of scar tissue during the healing process or at an early stage of the healing process (e.g. treatment of an open wound).

Sodium hypochlorite solutions have been used for the purposes of wound irrigation to disinfect a wound. Such solutions include Dakin's solution which has been used as an antiseptic, and typically comprises 0.4-0.5% sodium hypochlorite and buffering agents to provide a pH of 9-10. Modified forms of Dakin's solution have been prepared as antibacterial solutions to disinfect wounds.

GB2519774 and GB2527264 describe a hypochlorite solution for use in prevention or treatment of an inflammatory response in uncontaminated or non-infected surgical sites, wounds, trauma sites, internal inflammatory lesions or surface inflammatory lesions where there is no infection. The hypochlorite solution described therein may comprise sodium hypochlorite in a concentration range of 0.005-0.2 wt% and may further comprise sodium chloride in a concentration range of 0.5-1.5 wt%. Inflammatory conditions such as mouth ulcers, eczema and psoriasis are mentioned, and the treatment of the inflammatory response in an open fistula is exemplified. Neither GB2519774 nor GB2527264 contemplate use of the hypochlorite solution described therein for purposes other than mitigating the inflammation response, and do not contemplate prophylaxis of scar tissue.

There is a need to provide new treatments for the prevention of, or reduction in the formation of, scar tissue. There is also a need for new treatments for improving the appearance of scar tissue.

SUMMARY OF THE INVENTION

The inventors have surprisingly discovered that treating wounds with a hypochlorite solution comprising 0.01-0.2 wt% (about 100-2000 ppm by wt) is effective in the prophylactic treatment of scar tissue. Indeed, more particularly the inventors have discovered that by applying the hypochlorite solution described herein to new or recent wounds (that is to say wounds less than 10 days old), scar tissue formation can be dramatically reduced or even avoided. The inventors have further found that application of the hypochlorite solution leads to improved overall appearance of the wound area, and minimises the extent of the scar tissue. Indeed, the inventors have surprisingly discovered that the hypochlorite solution for use as described herein leads to formation of normal healthy tissue where scar tissue may normally be expected. Without wishing to be bound by theory, the inventors postulate that this formation of normal healthy tissue is promoted by the unexpected and unpredictable effects of the hypochlorite solution described herein on cytokines involved in scar tissue formation.

According to a first aspect of the present invention, there is provided a hypochlorite solution for use in the prophylactic treatment of scar tissue in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt). As described in more detail below, the inventors have surprisingly and unexpectedly discovered that the claimed hypochlorite concentrations modulate cytokines involved in the formation of scar tissue, and promote activity of cytokines linked to reducing scar formation. More particularly, the inventors have found that the hypochlorite solution described herein promotes interleukin (IL-10) activity, which is associated with reduced scar tissue formation. The inventors further demonstrate that the claimed solutions achieve reduction in scar formation in the clinic (see examples).

The prophylactic treatment may comprise, or consist of, topical administration of the hypochlorite solution to a mammal, preferably a human, in need thereof. More particularly, the administration of the hypochlorite solution may comprise topical administration of the hypochlorite solution to a particular area of a mammal, preferably a human, in need thereof where the particular area is a site of trauma, or a site of a disease or condition characterised by the abnormal formation of collagen. For example, the prophylactic treatment may comprise topical administration of the hypochlorite solution to a wound or site of trauma (e.g. trauma from surgery). For example, the prophylactic treatment may comprise topical administration of the hypochlorite solution to an area of the mammal, preferably a human, wherein said area is a site of a disease or condition characterised by the abnormal formation of collagen. The hypochlorite solution may be administered topically by irrigation, submerging or washing of said area for a period of time.

In embodiments, the prophylactic treatment may comprise administration of the hypochlorite solution to a wound, optionally wherein the wound is a trauma site or a surgical wound. As such, the scar tissue to be prophylactically treated may be scar tissue from healing of a wound, optionally wherein the wound is a trauma site or a surgical wound. The wound may be sutured or may be an open wound. The hypochlorite solution described herein is particularly effective in prophylactic treatment of open wounds, e.g. open wounds that have not yet closed by natural healing processes.

The prophylactic treatment may comprise administration of the hypochlorite solution to the wound during the period in which the wound is healing. On the first day of administration of the hypochlorite solution to the wound, the wound is optionally less than 10 days old, optionally less than 5 days old, optionally still less than 1 day old. For instance, on the first day of administration of the hypochlorite solution, the wound may be less than 24 hours old, optionally less than 12 hours old, and optionally less than 6 hours old. Preferably, the hypochlorite solution is administered to the wound immediately when the wound is fresh (i.e. within 1 hour or within 2 hours or within 3 hours of the wound being inflicted). The prophylactic treatment may comprise administration of the hypochlorite solution to the wound by topical administration.

The scar tissue may be selected from one or more of keloid scar tissue, hypertrophic scar tissue, and scar contractures The scar tissue to be prophylactically treated may be scar tissue caused by a disease or condition that is characterised by the abnormal production of collagen. Diseases or conditions characterised by the abnormal production of collagen may be referred to as collagen diseases or collagen conditions. Collagen diseases or conditions may be selected from the list including myocardial fibrosis and purpura fulminans. Collagen disease or conditions may be selected from pulmonary fibrosis, chronic obstructive pulmonary disease, and long COVID-19.

In embodiments, the mammal may have been identified as being at risk of developing a lung disease or lung condition which causes scarring of the lungs, optionally wherein the lung disease or lung condition is selected from pulmonary fibrosis, chronic obstructive pulmonary disease, and long COVID-19. For instance, the mammal may have been identified as being at risk of developing long COVID-19 following a positive diagnosis of COVID-19 infection. The prophylactic treatment may comprise administration of the hypochlorite solution to the lungs via inhalation.

In embodiments, the collagen disease or condition is not a respiratory condition or disease. In embodiments, the collagen disease or condition is not a respiratory condition or disease selected from acute respiratory distress syndrome (ARDS); asthma; bronchitis; chronic obstructive pulmonary disease (COPD); common cold; coronaviral diseases such as severe acute respiratory syndrome (SASS), COVID-19; cystic fibrosis; influenza; Middle East respiratory syndrome (MESS); pneumonia, such as viral pneumonia, bacterial pneumonia and ventilator-associated pneumonia; pulmonary fibrosis; rhinoviral diseases; sarcoidosis (e.g. affecting lungs); tuberculosis; or inflammation of lung tissue.

The prophylactic treatment may comprise administration of the hypochlorite solution to the mammal on consecutive days. For example, the administration of the hypochlorite solution may be for at least 2 consecutive days, optionally for at least 3 consecutive days, optionally at least 4 consecutive days, optionally at least 5 consecutive days, optionally at least 6 consecutive days, and optionally at least 7 consecutive days. For instance, the administration of the hypochlorite solution may be for at least 14 consecutive days, optionally at least 21 consecutive days, further optionally at least 30 consecutive days. Alternatively, the treatment may comprise administration of the hypochlorite solution on alternate days, for a period of at least 7 days, optionally at least 14 days, optionally at least 28 days.

The prophylactic treatment may comprise administration of the hypochlorite solution to the mammal at least once daily. The prophylactic treatment may comprise administration of the hypochlorite solution to the mammal at least twice daily (e.g. twice daily or three times daily). The prophylactic treatment may comprise administration of the hypochlorite solution to the mammal at least three-times daily (e.g. three times daily or four times daily). The prophylactic treatment may comprise administration of the hypochlorite solution to the mammal at least four times daily (e.g. four times daily or fives time daily). The prophylactic treatment may comprise administration of the hypochlorite solution to the mammal at least five times daily (e.g. five time daily or six times daily).

The hypochlorite solution may comprise hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt), wherein the hypochlorite is sodium hypochlorite.

The hypochlorite solution may comprise hypochlorite in a concentration range of about 0.01-0.1 wt% (about 100-1000 ppm by wt), more preferably about 0.015-0.075 wt% (about 150-750 ppm), even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt), most preferably about 0.04-0.06 wt% (about 400-600 ppm by wt). The hypochlorite concentration may be 0.045-0.055 wt%, for example 0.05 wt% (500 ppm).

The hypochlorite solution further comprises sodium chloride. The sodium chloride may be in a concentration range of about 0.2-3.0 wt%, optionally still about 0.3-1.5 wt%, further optionally in a concentration range of about 0.4-1.3 wt%.

The hypochlorite solution for use as described herein may further comprise sodium chloride a concentration range of about 0.5-1.2%, optionally in a concentration range of about 0.6-1.0% (e.g. 0.7-1.0%), and optionally still in a concentration range of about 0.8-1.0 wt%. The hypochlorite solution for use as described herein may further comprise 0.8 wt% sodium chloride. The hypochlorite solution for use as described herein may further comprise 0.85 wt% sodium chloride.

The hypochlorite solution for use as described herein may further comprise sodium chloride a concentration range of about 0.2-1.0%, optionally in a concentration range of about 0.3-0.8% (e.g. 0.3-0.7%), and optionally still in a concentration range of about 0.3-0.6 wt% (e.g. 0.3-0.5wt%). The hypochlorite solution for use as described herein may further comprise 0.4 wt% sodium chloride.

The hypochlorite solution may be an aqueous sodium hypochlorite solution comprising sodium hypochlorite, sodium chloride, and water to balance.

The hypochlorite solution may be an aqueous sodium hypochlorite solution consisting of sodium hypochlorite, sodium chloride, and water to balance. Advantageously, and without wishing to be bound by theory, it is thought that the hypochlorite solution consisting of the foregoing means that other components do not interfere with the function of cytokines involved in the wound healing process and scar tissue formation. As such, only the components of the hypochlorite solution described herein influence cytokine function, and thus advantageously reduce formation of scar tissue.

The hypochlorite solution may have a pH of from about 5-11, preferably about 6-10, more preferably about 7-9, even more preferably about 7-8.

The hypochlorite solution may be unbuffered. That is to say the hypochlorite solution may have an absence of stabilising agents, buffering agents, and the like. Advantageously, and without wishing to be bound by theory, it is thought that the hypochlorite solution being unbuffered means that stabilising agents, buffering agents, and the like to not interfere with the function of cytokines involved in the wound healing process. As such, only the components of the hypochlorite solution described herein influence cytokine function, and thus advantageously reduce formation of scar tissue.

The hypochlorite solution may be unbuffered, have a pH of from about 5-11, and comprise (or consist of) 0.01-0.2 wt% sodium hypochlorite, 0.2-3.0 wt% sodium chloride, and water to balance. The concentrations of sodium hypochlorite and sodium chloride may be as defined above in accordance with the first aspect of the present invention. For instance, the hypochlorite solution may be unbuffered, and comprise (or consist of) 0.045-0.055 wt% (e.g. 0.05 wt%) sodium hypochlorite, 0.8-1.0 wt% (e.g. 0.85 wt% or 0.8 wt%) sodium chloride and water to balance. For instance, the hypochlorite solution may be unbuffered, and comprise (or consist of) 0.045-0.055 wt% (e.g. 0.05 wt%) sodium hypochlorite, 0.3-0.5 wt% (e.g. 0.4 wt%) sodium chloride and water to balance.

Accordingly there is provided a hypochlorite solution for use in the prophylactic treatment of scar tissue in a mammal, preferably a human, comprising (or consisting of) 0.045-0.055 wt% (e.g. 0.05 wt%) sodium hypochlorite, 0.8-1.0 wt% (e.g. 0.85 wt% or 0.8 wt%) sodium chloride and water to balance, optionally wherein the treatment comprises topically administering the hypochlorite solution to an area of the mammal in need thereof at least once daily for a period of at least 30 seconds for at least 14 consecutive days.

Accordingly there is provided a hypochlorite solution for use in the prophylactic treatment of scar tissue in a mammal, preferably a human, comprising (or consisting of) 0.045-0.055 wt% (e.g. 0.05 wt%) sodium hypochlorite, 0.8-1.0 wt% (e.g. 0.85 wt% or 0.8 wt%) sodium chloride and water to balance, optionally wherein the treatment comprises administering the hypochlorite solution to the mammal in need thereof at least twice daily, preferably at least three-times daily, preferably still at least four-times daily, for a period of at least 30 minutes for at least 2 consecutive days.

Accordingly, there is provided a hypochlorite solution for use in the prophylactic treatment of scar tissue in a mammal, preferably a human, comprising (or consisting of) 0.045-0.055 wt% (e.g. 0.05 wt%) sodium hypochlorite, 0.3-0.5 wt% (e.g. 0.4 wt%) sodium chloride and water to balance, optionally wherein the treatment comprises topically administering the hypochlorite solution to an area of the mammal in need thereof at least twice a daily, preferably three-times daily, for a period of at least 5 minutes, preferably for a period of at least 30 minutes, for at least 21 consecutive days.

Also provided is a pharmaceutical composition for use in the prophylactic treatment of scar tissue in a mammal, more preferably a human, wherein the pharmaceutical composition comprises a hypochlorite solution as defined in accordance with the first aspect of the present invention.

Also provided is use of a hypochlorite solution as defined in the first aspect of the present invention in the preparation of a medicament for prophylactic treatment of scar tissue in a mammal, preferably a human. The treatment may be as defined in accordance with the first aspect of the invention.

Also provided is a method for prophylactic treatment of scar tissue in a mammal, preferably a human, comprising administering a therapeutically effective amount of a hypochlorite solution as defined in accordance with the first aspect of the present invention to a mammal in need thereof The treatment may be as defined in accordance with the first aspect of the invention.

Also provided is a method, for improving the appearance of scar tissue, the method comprising administering an amount of a hypochlorite solution as defined in accordance with the first aspect of the present invention to a mammal, wherein the method is a cosmetic method and the administration is topical administration.

According to a second aspect of the invention, there is provided a hypochlorite solution for use in the prevention or treatment of scar tissue in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt). The hypochlorite solution may be as defined in accordance with the first aspect of the invention. The prevention or treatment may be as defined in accordance with the first aspect of the invention. For example, the prevention or treatment of scar tissue may be in the treatment of a wound. The prevention or treatment of scar tissue may be in the prophylactic treatment of disease or condition characterised by abnormal formation of collagen. The prevention or treatment of scar tissue may be in the treatment of purpura fulminans. The treatment may reduce the formation of scar tissue.

According to a third aspect of the invention, there is provided a hypochlorite solution for use in the treatment of purpura fulminans in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt). The hypochlorite solution may be as defined in accordance with the first aspect of the invention. The treatment may be as defined in accordance with the first aspect of the invention.

According to a fourth aspect of the invention, there is provided a hypochlorite solution for use in the prevention or treatment of a disease or condition characterised by the abnormal production of collagen in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt). The hypochlorite solution may be as defined in accordance with the first aspect of the invention. The treatment may be as defined in accordance with the first aspect of the invention. There is also provided a method of preventing or treating a disease or condition characterised by the abnormal production of collagen (collagen diseases), the method comprising administering a therapeutically effective amount of the hypochlorite solution to a mammal, preferably a human, in need thereof, wherein the hypochlorite solution is in accordance with the first aspect of the invention. The treatment may be as defined in accordance with the first aspect of the invention.

According to a fifth aspect of the invention, there is provided a method of reducing the production of collagen in a fibroblast cell, the method comprising contacting the cell with a hypochlorite solution comprising hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt) for a period of time sufficient to decrease activity of interleukin-6 (IL-6) and to maintain activity of inerleukin-10 (IL-10). In embodiments, the method is preferably not a method of treatment practised on the human or animal body (e.g. is an in vitro or ex vivo method). There is also provided a method of preventing or treating a disease or condition that would benefit from reducing the production of collagen by fibroblast cells, the method comprising administering the hypochlorite solution to a mammal, preferably a human, in need thereof, wherein the hypochlorite solution is in accordance with the first aspect of the invention. The treatment may be as defined in accordance with the first aspect of the invention.

According to a sixth aspect of the invention, there is provided a method of controlling differentiation of a fibroblast cell, the method comprising contacting the cell with a hypochlorite solution comprising hypochlorite in a concentration range of about 0.010.2 wt% (about 100-2000 ppm by wt) for a period of time sufficient to decrease activity of interleukin-6 (IL-6) and to maintain activity of inerleukin-10 (IL-10). In embodiments, the method is preferably not a method of treatment practised on the human or animal body (e.g. is an in vitro or ex vivo method). There is also provided a method of preventing or treating a disease or condition that would benefit from controlling differentiation of fibroblast cells, the method comprising administering the hypochlorite solution to a mammal, preferably a human, in need thereof, wherein the hypochlorite solution is in accordance with the first aspect of the invention. The treatment may be as defined in accordance with the first aspect of the invention.

DESCRIPTION OF THE FIGURES

The invention is further described in the following non-limiting figures: Figure 1 shows IL-6 cells in Example 1 dialysed against a control saline solution (0.85 wt%) to determine functionality of cytokine.

Figure 2 shows IL-6 cells in Example 1 dialysed against a solution of Composition 1 to determine functionality of cytokine.

Figure 3 shows IL-6 cells in Example 1 dialysed against a solution of Composition 2 to determine functionality of cytokine.

Figure 4 shows IL-10 cells in Example 2 dialysed against a control saline solution (0.85 wt%) to determine functionality of cytokine.

Figure 5 shows IL-10 cells in Example 2 dialysed against a solution of Composition 1 to determine functionality of cytokine.

Figure 6 shows IL-10 cells in Example 2 dialysed against a solution of Composition 2 to determine functionality of cytokine.

Figure 7 shows survival of MC9 cells following exposure of IL-10 to A (Composition 1) and B (Composition 2).

Figure 8 shows survival of B9 cells following exposure of IL-6 to A (Composition 1) and B (Composition 2).

Figure 9 is a photograph of the ankle area of the patient according to Example 5.

Figure 10 are photographs of the outside left thigh of the patient according to Example 8. Figure 10A was taken before treatment, Figure 10B was taken during treatment, and Figure 10C was taken after 14 days of treatment.

DETAILED DESCRIPTION

The following embodiments apply to all aspects of the present invention.

The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects or embodiment or embodiments unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

The term "treating", as used herein, unless otherwise indicated, means reversing, attenuating, alleviating or inhibiting the progress of the disease or condition to which such term applies, or one or more symptoms of such disorder or condition.

The term 'prophylactic treatment', as used herein means treatment designed to prevent the condition from occurring or minimize the likelihood of a condition occurring. The prophylactic treatment of scar tissue encompasses the prevention of the formation of scar tissue as well as reduction (e.g. in surface area and/or level of severity) of the formation of scar tissue.

The term "scar tissue" refers to tissue which is formed during the wound healing process or as a result of a disease or condition that causes scarring of normal tissue.

Scar tissue forms as a direct consequence of trauma to normal tissue e.g. the skin. Fibrosis is the process by which new tissue is formed in response to a wound, leading to tissue remodeling and the formation of scar tissue. Fibrosis may therefore be used in the art to mean the process by which scar tissue is formed. Fibrosis is facilitated by fibroblast cells. As such, wherever prophylactic treatment of scar tissue or treatment of scar tissue is referred to herein, those skilled in the art will understand that prevention or treatment of fibrosis is also contemplated.

A disease or condition characterised by the abnormal formation of collagen may be any disease or condition which causes scarring to tissue. Such diseases and conditions may be selected from myocardial fibrosis and purpura fulminans. Such diseases and conditions may include pulmonary fibrosis, chronic obstructive pulmonary disease, and long COVID-19 The term "open wound" refers to an injury of the skin, wherein the skin is punctured, torn or cut, and exposes internal body tissue. The term encompasses incisions, lacerations, abrasions, punctures, and gunshots. The term refers to the wound before it is closed by natural healing processes.

"Patient' includes humans, non-human mammals (e.g., dogs, cats, rabbits, cattle, horses, sheep, goats, swine, deer, and the like) and non-mammals (e.g., birds, and the like).

"wt%" as used herein refers to the weight by mass relative to the total weight of the hypochlorite solution.

Without wishing to be bound by theory, it is thought that the hypochlorite solution of the present invention acts on the known initiators, mediators and regulators of scar tissue formation. The solution of the invention is thought to inhibit the release of inflammatory agents (e.g. cytokines and chemokines) from blood platelets, but does not prevent the platelets from aggregating. It is thought that the solution also attenuates the effect of cytokines, chemokines and other inflammatory mediators. Proof of concept that such an effect can be exploited in the prophylactic treatment scar tissue has been demonstrated in the Examples described herein. It has also been found that such an effect can be provided without serious safety issues, as demonstrated in the Examples described herein.

The inventors have surprisingly and unexpectedly discovered that the hypochlorite solution as described herein can selectively affect the function of particular anti-inflammatory cytokines. The data described herein demonstrates that the hypochlorite solution as described herein causes loss of IL-6 function in vitro. Conversely, the hypochlorite solution as described herein led to no significant change in IL-10 function in vitro.

As such, the hypochlorite solution of the present invention can disrupt normal cytokine activity in vitro thus providing a means of controlling cytokine-dependent cell signalling pathways. IL-6 has been implicated in promoting formation of scar tissue and fibrosis (Johnson et at DOI: 10.3390/biomedicines8050101). IL-10 has been implicated in regulation of fibrogenic cytokines, the extracellular matrix, and promotion of fibroblast function. IL-10 has therefore been shown to have a role in tissue remodelling and reducing scar formation (King eta! DOI 10.1089/wound.2013.0461). Without wishing to be bound by theory, these data indicate that use of the hypochlorite solution according to the present invention causes loss of IL-6 function whilst maintaining IL-10 function, which signals a net negative effect on scar tissue formation.

The inventors have found that hypochlorite (001-) solutions are eminently suitable at the concentrations described. Preferably, the hypochlorite solution described herein does not comprise chlorite (C102-).

The hypochlorite solution for use as described herein may be administered topically to an area of the mammal in need thereof (e.g. tissue that is the site of trauma). The hypochlorite solution may be provided as a solution and topically applied by means of irrigating, submerging or washing the tissue to be treated (e.g. a wound) in the hypochlorite solution for a period of time. The hypochlorite solution may be provided in the form of a cream or gel, and applied directly to the tissue to be treated (e.g. a wound).

The hypochlorite solution may be topically administered for a period of about 30 seconds to about 90 minutes. Preferably, the hypochlorite solution is topically administered 1 minute to about 90 minutes, about 5 minutes to about 90 minutes, about 10 minutes to about 90 minutes, about 15 minutes to about 90 minutes, about 20 minutes to about 90 minutes, about 30 minutes to about 90 minutes, about 45 minutes to about 90 minutes, about 60 minutes to about 90 minutes, about 30 seconds to about 60 minutes, about 30 seconds to about 45 minutes, about 30 seconds to about 30 minutes, about 30 seconds to about 20 minutes, about 30 seconds to about 15 minutes, about 30 seconds to about 10 minutes, about 30 seconds to about 5 minutes or about 30 seconds to about 1 minute.

The hypochlorite solution may be topically administered for at least 5 minutes, optionally at least 10 minutes, optionally still at least 15 minutes. The tissue to be treated (e.g. a wound) may be irrigated with, submerged in, or washed with the hypochlorite solution for at least 20 minutes, optionally at least 30 minutes.

The hypochlorite solution for use as described herein may be administered topically at least once daily. For example, the prophylactic treatment may comprise topical administration of the hypochlorite solution at least twice daily, optionally at least three-times daily, and optionally still at least four times daily.

The hypochlorite solution may be administered topically for 2 to 30 consecutive days, optionally for 5 to 28 consecutive days, optionally still from 7 to 14 consecutive days.

Alternatively, the treatment may comprise topical administration of the hypochlorite solution on alternate days, for a period of 2 to 30 consecutive days, optionally 5 to 28 consecutive days, optionally still 7 to 14 consecutive days.

In embodiments, the hypochlorite solution is topically administered for at least 5 consecutive days at least once daily, optionally at least 7 consecutive days at least once daily, and optionally still at least 14 consecutive days at least once daily (e.g. twice daily).

The hypochlorite solution for use as described herein may be administered by inhalation e.g. via a nebulizer. The type of nebulizer is not particularly limited provided that it is able to break up the hypochlorite solution into aerosol droplets for inhalation. The nebulizer may be connected to an outlet configured to deliver the hypochlorite solution to a patient via the nose and/or mouth. For example, the outlet may be a mouthpiece or a facemask. The hypochlorite solution for use as described herein may be administered by inhalation e.g. via an inhaler. For example, the inhaler may be a metered-dose inhaler. The metered-dose inhaler may be configured to deliver a set dose of the hypochlorite solution on each actuation of the metered-dose inhaler. The hypochlorite solution for use as described herein may be provided in a medicament container that is suitable for use with an inhalation device. Medicament containers may include cartridges or canisters suitable for use with inhalation devices such as an inhaler or nebuliser. The hypochlorite solution for use as described herein may be packaged into a cartridge containing a propellant, thus forming a cartridge comprising a hypochlorite solution and a propellant. Similarly, the hypochlorite solution may be packaged into a canister container a propellant, thus forming a canister comprising a hypochlorite solution and a propellant. The propellant may be a chlorofluorocarbon or a hydrofluoroalkane, or the like. The cartridge or canister may be used with an inhaler. The cartridge or canister may be detachable from the inhaler. The cartridge or canister may be attached to the inhaler prior to use.

The hypochlorite solution may be administered via inhalation continuously. For example, such continuous administration via inhalation may be applied to ventilated patients, patients in a hospital setting, sedated patients, or patients in a coma or induced coma. In some cases, the administration may be for a period of about 30 seconds to about 90 minutes. Preferably, the hypochlorite solution is administered via inhalation for a period of about 1 minute to about 90 minutes, about 5 minutes to about 90 minutes, about 10 minutes to about 90 minutes, about 15 minutes to about 90 minutes, about 20 minutes to about 90 minutes, about 30 minutes to about 90 minutes, about 45 minutes to about 90 minutes, about 60 minutes to about 90 minutes, about 30 seconds to about 60 minutes, about 30 seconds to about 45 minutes, about 30 seconds to about 30 minutes, about 30 seconds to about 20 minutes, about 30 seconds to about 15 minutes, about 30 seconds to about 10 minutes, about 30 seconds to about 5 minutes or about 30 seconds to about 1 minute. The hypochlorite solution may be administered via inhalation once, twice, thrice or four times daily.

Preferably, the hypochlorite solution is administered once daily.

The hypochlorite solution may be administered in a cycle comprising a treatment period of administration of the hypochlorite solution once, twice, thrice or four times daily for a period of a few days (e.g. about 1, 2, 3, 4, 5, 6 or 7 days) to a few weeks (e.g. about 1, 2, 3 or 4 weeks), optionally followed by a period where the hypochlorite solution is not administered for a period of a few days (e.g. about 1, 2, 3, 4, 5, 6 or 7 days) to a few weeks (e.g. about 1, 2, 3 or 4 weeks). The cycle may be repeated at least twice. For example, the cycle may be repeated twice, thrice, four times, five times, six times, seven times, eight times, nine times, ten times, etc. The hypochlorite solution for use as described herein is preferably an aqueous solution.

Preferably, the hypochlorite solution contains hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt), more preferably about 0.01-0.1 wt% (about 100-1000 ppm by wt), even more preferably about 0.015-0.075 wt% (about 150750 ppm), yet even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt), most preferably about 0.04-0.06 wt% (about 400-600 ppm by wt). For example, the hypochlorite solution contains hypochlorite at about 0.05 wt% (about 500 ppm by wt).

The hypochlorite solution for use as described herein may further comprise sodium chloride, optionally in a concentration range of about 0.2-3.0 wt%, optionally still about 0.3-1.5 wt%, further optionally in a concentration range of about 0.4-1.3 wt%. The hypochlorite solution for use as described herein may further comprise sodium chloride a concentration range of about 0.5-1.2%, optionally in a concentration range of about 0.6-1.0% (e.g. 0.7-1.0%), and further optionally in a concentration range of about 0.81.0 wt% (e.g. 0.8-0.9 wt%). The hypochlorite solution for use as described herein may further comprise 0.85 wt% sodium chloride. The hypochlorite solution for use as described herein may further comprise sodium chloride a concentration range of about 0.2-1.0%, optionally in a concentration range of about 0.3-0.8% (e.g. 0.3-0.7%), and optionally still in a concentration range of about 0.3-0.6 wt% (e.g. 0.3-0.5wt%). The hypochlorite solution for use as described herein may further comprise 0.4 wt% sodium chloride.

The hypochlorite solution for use as described herein may have a pH of from about 511, preferably about 6-10, more preferably about 7-9, even more preferably about 7-8. In some embodiments, the pH may be about 5-6, about 6-7, about 8-9, about 9-10, or about 10-11. In embodiments, the pH of the hypochlorite solution is greater than 7.5.

For example, in embodiments, the pH of the hypochlorite solution from 10-11. Alkaline pHs are generally preferred to ensure the presence of hypochlorite ion (c10). Acidification of hypochlorites generates hypochlorous acid which is a different chemical entity.

Typically, when used, the pH of the hypochlorite solution is within a range encountered in normal physiology and disease processes. This is because the hypochlorite solution preferably auto-adjusts pH.

The hypochlorite solution for use as described herein may be unbuffered. In preferred embodiments, the hypochlorite solution is unbuffered. In other words, the hypochlorite solution is free of buffer agents. The hypochlorite solution is preferably free of stabilising agents. The hypochlorite solution is therefore free of other agents which may otherwise disrupt the beneficial effects described herein on IL-6 and IL-10 activity.

Beneficial effects for the prevention or treatment of scar tissue are particularly noticeable where the patient is treated with a solution which has a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt), yet more preferably about 0.01-0.1 wt% (about 100-1000 ppm by wt), even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt) sodium hypochlorite; sodium chloride in a concentration range of about 0.3-1.5 wt%, optionally in a concentration range of about 0.4-1.3 wt%, optionally still in a concentration range of about 0.5-1.2%, further optionally in a concentration range of about 0.8-1.0 wt%; wherein the solution is unbuffered. Yet more preferably the solution consists of about 0.01-0.2 wt% (about 100-2000 ppm by wt), yet more preferably about 0.01-0.1 wt% (about 100-1000 ppm by wt), even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt) sodium hypochlorite; sodium chloride in a concentration range of about 0.3-1.5 wt%, optionally in a concentration range of about 0.4-1.3 wt%, optionally still in a concentration range of about 0.5-1.2%, further optionally in a concentration range of about 0.8-1.0 wt%; wherein the solution is unbuffered.

Beneficial effects for the prevention or treatment of scar tissue are particularly noticeable where the patient is treated with a solution which has a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt), yet more preferably about 0.01-0.1 wt% (about 100-1000 ppm by wt), even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt) sodium hypochlorite; sodium chloride in a concentration range of about 0.3-1.5 wt%, optionally in a concentration range of about 0.4-1.3 wt%, optionally still in a concentration range of about 0.5-1.2%, further optionally in a concentration range of about 0.8-1.0 wt%; wherein the solution is buffered to a pH of from about 5-11, preferably about 6-10.

For example, a hypochlorite solution comprising 0.85% sodium chloride and 0.05% (500 ppm) sodium hypochlorite w/w has been found to be very beneficial in preventing and treating scar tissue in a patient, preferably a mammal, more preferably a human.

For example, a hypochlorite solution comprising 0.4% sodium chloride and 0.05% (500 ppm) sodium hypochlorite w/w has been found to be very beneficial in preventing and treating scar tissue in a patient, preferably a mammal, more preferably a human. A hypochlorite solution 0.4% sodium chloride and 0.05% (500 ppm) sodium hypochlorite w/w has been found to be very beneficial for use in the treatment of purpura fulminans.

Preferably the hypochlorite solution should be very pure. Preferably the hypochlorite solution is generated electrolytically to ensure its purity as well as its safety and effectiveness. In embodiments, the hypochlorite solution comprises hypochlorite (e.g. sodium hypochlorite), water, and optionally sodium chloride in a purity of greater than %, optionally greater than 95 wt%, optionally still greater than 98 wt%, further optionally greater than 99 wt%, relative to the total weight of the hypochlorite solution.

The hypochlorite solution may be produced from a concentrated hypochlorite solution to be diluted before use. Preferably, the concentrated hypochlorite solution to be diluted before use is a concentrated sodium hypochlorite solution. The concentration of hypochlorite in the concentrated hypochlorite solution may be in the range of about 0.5 to 3 wt%. Furthermore, the concentrated hypochlorite solution may be buffered to a pH of from about 9-15, preferably about 11-13. Alternatively, the concentrated hypochlorite solution may be unbuffered. The concentrated hypochlorite solution may be a stabilised sodium hypochlorite solution at 1% or 2% sodium hypochlorite, e.g. a disinfectant known as "Milton's Solution" comprising sodium chloride. The diluted hypochlorite solution may be a 2.5% -10% solution of Milton's solution diluted in water where the disinfectant solution is 2% sodium hypochlorite. The sodium chloride in the solution is typically at a concentration of 16.5%. Thus, the ratio by volume of the hypochlorite solution to water may be in the range of from 1 to 10 to 1 to 40. Alternatively, the dilute hypochlorite solution may be a 5% to 20% solution of Milton's solution diluted in water where the disinfectant solution is 1% sodium hypochlorite. In this case, the ratio by volume of the hypochlorite solution to water may be in the range of from 1 to 5 to 1 to 20.

In both cases, the predetermined amount of water and the predetermined amount of sodium hypochlorite solution may be such that the dilute disinfectant solution may be a stabilised sodium hypochlorite solution where the sodium hypochlorite is in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt), more preferably about 0.01-0.1 wt% (about 100-1000 ppm by wt), even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt) sodium hypochlorite. The action of the sodium hypochlorite solution can provide stabilisation of the dilute disinfectant solution.

A device suitable for preparing a hypochlorite solution for use in the present invention is described in WO-A-2011/128862.

Various embodiments and optional features are described above. It will be appreciated that these embodiments and features can be combined in all viable permutations.

While the foregoing disclosure provides a general description of the subject matter encompassed within the scope of the present invention, including methods, as well as the best mode thereof, of making and using this invention, the following examples are provided to further enable those skilled in the art to practice this invention and to provide a complete written description thereof However, those skilled in the art will appreciate that the specifics of these examples should not be read as limiting on the invention, the scope of which should be apprehended from the claims and equivalents thereof appended to this disclosure. Various further aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure.

EXAMPLES

Examples 1 and 2 -In vitro studies on cytokine function Materials: * Solution of Composition 1 -Sodium hypochlorite at 0.05 wt%, in saline 0.85 wt% * Solution of Composition 2 -Sodium hypochlorite at 0.1 wt%, in saline at 0.8 wt% * Solution of Composition 3 -Sodium hypochlorite at 0.05 wt%, in saline at 0.4 wt% * IL-6 Dependent cell line B9 (Catalogue number 12121201, Mouse B cell hybridoma) * IL-10 Dependent cell line MC9 (ARCC CRL-8306TM, Mouse liver mast cell) * PrestoBlue® (cell-permeable fluorescent compound for use in cell-viability assays) Method: Plasma samples were obtained from a volunteer and the cells were separated from the plasma. The plasma samples were placed in dialysis tubing whose pore size was less than the molecular weight of the cytokines. This was placed in 1000x excess (i.e. 1 ml in 1 L, 2 ml in 2 L etc.) of dialysis media.

The dialysis media was in either saline solution (0.85 wt%) as a control, Composition 1 or Composition 2 and was extracted after 5 minutes, 15 minutes, 30 minutes, 45 minutes and 60 minutes and then analysed. The cytokine functionality was thus determined.

Cytokine Function: Functional cell assays were carried out with patient plasma to investigate its ability to support the survival of cytokine dependent cell lines.

The serum was spiked with human recombinant cytokines. Heat-inactivated fetal bovine serum was used and was spiked with human recombinant IL-6 and IL-10 at 100 ng/ml.

The serum samples were dialysed with either 0.85 wt% saline solution, Composition 1 or Composition 2, as described above.

IL-6 function was assessed by determining the ability to maintain the growth of the IL-6 dependent cell line B9.

IL-10 Function was assessed by the ability to maintain the growth of the IL-10 dependent cell line MC9.

Cell viability was measured using fluorescence. A cell-permeable non-fluorescent compound was added to the assay. Viable cells maintain a reducing environment, which reduced the fluorescent compound, giving a colour change which fluoresces at 560 nm.

The degree of fluorescence was measured and directly correlates with the number of viable cells. The results are shown in Figures 1 to 8.

In some experiments, a high level of cytokine long/m1) caused a decrease in cell viability. Without wishing to be bound by theory, the inventors postulate that this may be due to a prozone-like effect at high cytokine levels and/or that high levels of cytokine may cause cell death or the inhibition of cell metabolism in this system.

Example 1 -IL6

Figures 1 to 3 show the results from the cell-survival assay of the IL-6 spiked-serum samples dialysed against a control saline solution (Figure 1), Composition 1 (Figure 2) and Composition 2 (Figure 3).

In these graphs, the line describing the Pos/Neg boundary indicates a value which is the mean of the negative control wells (no added cytokine, n=16) +3 standard deviations above this mean. Everything above this value is considered positive.

Figures 2 and 3 show that dialysis of the serum samples with Composition 1 or Composition 2 of the present invention and leads to a loss of function of the IL-6 molecule when measured in the cell survival assay.

Example 2-IL1 0

Figures 4 to 6 show the results from the cell survival assay of the IL-10 spiked-serum samples dialysed against a control saline solution (Figure 4), Composition 1 (Figure 5) and Composition 2 (Figure 6).

The experimental data suggests that with dialysis of the serum samples with Compositions 1 or 2, IL-10 remains functional albeit with a slight loss of function of the IL-10 molecule when measured in the cell survival assay. IL-10 therefore remains functional as the loss of function is within expected range for an in vitro analysis with remaining net survival.

To evaluate this further, the data was analysed to look at the cell survival seen following exposure to Composition 1 or Composition 2 as a percentage of that achieved by the same quantity of cytokine following dialysis of 0.85 wt% saline solution (Figure 7) and the results were compared with those obtained for IL-6 analysed in the same way (Figure 8).

It can be seen from Figure 7 that IL-10 receptor binding is retained ensuring the survival of MC9 cells. In contrast, in Figure 8, there is almost a complete loss of function of IL-6 after 15 minutes exposure of Composition 1 or Composition 2. With complete loss of IL-6 function and negligible impact on IL-10 function, the combined effect is significantly anti-inflammatory and anti-scar tissue formation. This comprises removal of cytokine action that promotes formation of scar tissue and a relative increase in cytokine action that mitigates or reduces the formation of scar tissue. There is therefore a net negative effect on scar tissue formation. In other words, there is a net anti-fibrosis effect.

Without wishing to be bound by theory, in the context of fibrosis, IL-6 may act as a pro-inflammatory and pro-fibrosis agent in opposition to the anti-inflammatory and anti-fibrosis action of IL-10. Loss of IL-6 function therefore (at least partially) attenuates IL-6's opposing effect on IL-10 function and IL-10's associated downstream effects. The ratio of IL-6 and IL-10, or increase in relative levels of IL-10 may therefore predict the likelihood of scar tissue formation. For instance, King et al (Advances in Wound Care, Vol. 3, No.4, p.315) that IL-10 has been associated with wound healing and reduced scar formation. Additionally, Xi et a/ (2017 PLoS 2017 12(6)) describes that IL-10 may be used as a marker for predicting clinical outcome in patients with sepsis-induced immunosuppression.

Without wishing to be bound by theory, it is thought that the hypochlorite solutions according to the present invention, including Compositions 1 and 2, may assist in scar prophylaxis by promoting IL-10 function and reducing IL-6 function, thereby attenuating or removing the mitigating effects of IL-6 on IL-10 function.

Example 3 -Facial Laceration -In vivo patient efficacy studies Female. 3' decade. Several facial lacerations around the left eye and nose following a bicycle accident. Treatment comprised topical administration of aqueous sodium hypochlorite solution in saline (NaOCI: 0.05 wt% (500 ppm), NaCI: 0.85 wt%) daily for 14 consecutive days. Gauze was soaked in the aqueous sodium hypochlorite solution and placed on the lacerations. Facial lacerations fully healed within four weeks without any evidence of scar tissue or skin discoloration.

Example 4 -Lip (Buccal Mucosa) Laceration -In vivo patient efficacy studies Female. 3" decade. Lacerations to inside of the upper and lower lips following a bicycle accident, which developed into canker sores / mouth ulcers immediately after the accident. Treatment comprised topical administration of aqueous sodium hypochlorite solution in saline (NaOCI: 0.05 wt% (500 ppm), NaCI: 0.85 wt%) daily for 14 consecutive days. The aqueous sodium hypochlorite solution was used as a mouth wash daily. Mouth ulcers fully healed within four weeks without any evidence of scar tissue or tissue discoloration.

Example 5-Surgical Trauma -In vivo patient efficacy studies Female. 7th decade. Surgical trauma following surgery to fibula-side of left ankle to remove an internal fixation plate and screws. Treatment comprised suturing the wound immediately after surgery immediately followed by topical administration of aqueous sodium hypochlorite solution in saline (NaOCI: 0.05 wt% (500 ppm), NaCI: 0.85 wt%) daily for 14 consecutive days. Gauze was soaked in the aqueous sodium hypochlorite solution and placed on the trauma site. The lacerations fully healed within four weeks with a very light and thin scar line remaining (Figure 9).

Example 6 -Intra-oral Surgical Trauma -In vivo patient efficacy studies Male. 3 decade. Multiple intra-oral trauma sites following dental surgery. Patient had several teeth extracted, leaving bones exposed. Patient presented with poor healing two weeks after surgery and extreme pain. Patient was enrolled in study. Treatment comprised topical administration of aqueous sodium hypochlorite solution in saline (NaOCI: 0.05 wt% (500 ppm), NaCI: 0.85 wt%) daily for 14 consecutive days. The aqueous sodium hypochlorite solution was used as a mouth wash daily. Patient reported alleviation of symptoms, improved healing, and additionally ceased to take painkillers within 1 week of starting treatment. The intra-oral trauma sites fully healed within four weeks without any evidence of scar tissue or tissue discoloration.

Example 7-Lonq-COVID 19 -In vivo patient efficacy studies Treatment comprised administration of aqueous sodium hypochlorite solution in saline (NaOCI: 0.05 wt% (500 ppm), NaCI: 0.85 wt% -referred to in Example 7 as Composition 3), delivered by nebulizer.

Each patient enrolled had previously tested positive for COVID-19, and was suffering from symptoms of 'Long COVID-19' for at least 1-month from the date of a positive COVID-19 test. Composition 3 was administered to each patient by nebuliser for the time periods indicated in the table below. Frequency of inhalation is indicated as (number of times per day x duration of each treatment session). Where administration was 4 times daily, Composition 3 was administered every 6 hours. Where administration was 3 times daily, Composition 3 was administered every 8 hours.

For patients 1-4, the treatment was administered at the indicated frequency on consecutive days until the patient reported no symptoms. Treatment was administered at the indicated frequency for 21 consecutive days for patient 5, and for 7 consecutive days for patient 6.

Patient Age Gender #Vaccine Doses Long Covid Duration (#Months) Frequency of Symptom Free After #Days to no Comments inhalation Treatment symptoms 1 19 F 3 1.5 3x30 mins Y 4 Full recovery; Continued treatment 2 41 M 3 6 3x30 mins y 7 Full recovery; Back to gym 3 54 M 3 6 4x30 mins Y 4 90% recovery; Asthma improved 4 74 M 3 1.5 2x30 mins Y 2 recovery Rapid full 41 M 3 24 3x30 mins N N/A Partial recovery; Continued treatment 6 56 F 3 12 3x 30 mins N N/A No significant improvement #: Number; Vaccine Doses: Doses of a UK approved vaccine received by the patient prior to enrolment in study; Following treatment with composition 3, long COVID-19 symptoms were alleviated in patients 1-4, whom had been suffering with long COVID-19 for 6 months or less. Two patients made a full recovery from long COVID-19 (patients 1 and 2), and one patient made a near full (90%) recovery with mild asthma symptoms remaining (patient 3).

In contrast, following treatment with composition 3, long COVID-19 symptoms persisted in patients 5 and 6 whom had been suffering with long COVID-19 for 12 months or more. One patient (patient 5), whom had been signed off from work due to the debilitating effects of long COVID-19, had been suffering with the disease for 24 months and following treatment made a partial recovery with some alleviation of symptoms. Another patient (patient 6) who had been suffering with long COVID-19 for 12 months reported no substantive benefit after 7 days of treatment, and was confirmed as having suffered scarring to the lungs as a result of COVID-19 infection.

These data indicate that Composition 3 administered via inhalation is an effective treatment for symptoms of long COVID-19. Without wishing to be bound by theory, it is thought that patients who suffer with long COVID-19 for extended periods (e.g. longer than 6 months) suffer significant damage and/or scarring to the lungs. These data therefore indicate that where long COVID-19 patients are treated in the early stages of the disease (i.e. treating patients 6 months or less from the date of a positive COVID19 test), that Composition 3 prevents significant scarring to the lungs. In contrast, where significant scarring has already occurred (i.e. treating patients 12 months or more from the date of a positive COVID-19 test), Composition 3 is less effective in treating long COVID-19, but may still provide some therapeutic benefit. Again, without wishing to be bound by theory, it is thought that this partial therapeutic benefit may arise from reducing scar tissue in the lungs of the patient.

Example 8 -purpura fulminans -In vivo patient efficacy studies Female. 1st Decade. Patient admitted to hospital with varicella-associated purpura fulminans, a rare condition associated with a high mortality, amputations and scarring to tissue. The patient developed large purpuric skin lesions, which may become necrotic lesions, following admission to hospital. Treatment comprised bathing the patient in an aqueous sodium hypochlorite solution according to composition 3 (NaOCI: 0.05 wt% (500 ppm), NaCI: 0.4 wt %) three-times daily (every 8 hours) for 30 minutes each time. Treatment was carried out for 21 consecutive days. The purpuric skin lesions healed fully without any remaining indication of scarring. The patient made a full recovery without any scarring to the tissue. Figures 10A-10C are images of a large purpuric skin lesion on the patient's upper left leg. Figure 10A shows the lesion before treatment, Figure 10B shows the lesion during treatment, and Figure 10C shows the lesion after 14 days of treatment. At 21 days, the lesions had fully healed.

Claims

CLAIMS: 1. A hypochlorite solution for use in the prophylactic treatment of scar tissue in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt).
2. A hypochlorite solution for use according to claim 1, wherein the prophylactic treatment comprises topical administration of the hypochlorite solution.
3. A hypochlorite solution for use according to claim 1 or claim 2, wherein the prophylactic treatment comprises administration of the hypochlorite solution to a wound, optionally wherein the wound is a trauma site or a surgical wound.
4. A hypochlorite solution for use according to claim 3, wherein the wound is sutured or an open wound.
5. A hypochlorite solution for use according to claim 3 or claim 4, wherein the prophylactic treatment comprises administration of the hypochlorite solution to the wound during the period in which the wound is healing.
6. A hypochlorite solution for use according to any one of claims 3 to 5, wherein on the first day of administration of the hypochlorite solution to the wound, the wound is less than 10 days old, optionally wherein the wound is less than 5 days old, optionally still wherein the wound is less than 1 day old.
7. A hypochlorite solution for use according to any one of claims 1 to 6, wherein the scar tissue is selected from one or more of keloid scar tissue, hypertrophic scar tissue, and scar contractures.
8. A hypochlorite solution for use according to claim 1, wherein the prophylactic treatment is treatment of a disease or condition characterised by the abnormal production of collagen (collagen diseases), optionally wherein the mammal has been identified as being at risk of developing a lung disease or lung condition which causes scarring of the lungs, optionally wherein the lung disease or lung condition is selected from pulmonary fibrosis, chronic obstructive pulmonary disease, and long COVID-19.
9. A hypochlorite solution for use according to claim 8, wherein the prophylactic treatment comprises administration of the hypochlorite solution to the lungs via inhalation.
10. A hypochlorite solution for use according to any one of claims 1 to 9, wherein the prophylactic treatment comprises administration of the hypochlorite solution to the mammal on consecutive days.
11. A hypochlorite solution for use according to any one of claims 1 to 10, wherein the prophylactic treatment comprises administration of the hypochlorite solution to the mammal at least once daily, optionally at least twice daily.
12. A hypochlorite solution for use according to any one of claims 1 to 11, wherein the hypochlorite is sodium hypochlorite.
13. A hypochlorite solution for use according to any one of claims 1 to 12, wherein the hypochlorite is in a concentration range of about 0.01-0.1 wt% (about 100-1000 ppm by wt), more preferably about 0.015-0.075 wt% (about 150-750 ppm), even more preferably about 0.025-0.075 wt% (about 250-750 ppm by wt), most preferably about 0.04-0.06 wt% (about 400-600 ppm by wt).
14. A hypochlorite solution for use according to any one of claims 1 to 13, wherein the hypochlorite solution further comprises sodium chloride.
15. A hypochlorite solution for use according to claim 14, wherein the sodium chloride is in a concentration range of about 0.2-3.0 wt%, optionally 0.3-1.5 wt%, optionally still in a concentration range of about 0.4-1.3 wt%.
16. A hypochlorite solution for use according to any one of claims 1 to 15, wherein the hypochlorite solution is an aqueous sodium hypochlorite solution comprising sodium hypochlorite, sodium chloride, and water to balance, optionally wherein the hypochlorite solution is an aqueous sodium hypochlorite solution consisting of sodium hypochlorite, sodium chloride, and water to balance.
17. A hypochlorite solution for use according to any one of claims 1 to 16, wherein the hypochlorite solution has a pH of from about 5-11, preferably about 6-10, more preferably about 7-9, even more preferably about 7-8.
18. A hypochlorite solution for use according to any one of claims 1 to 17, wherein the hypochlorite solution is unbuffered.
19. A pharmaceutical composition for use in the prophylactic treatment of scar tissue in a mammal, more preferably a human, wherein the pharmaceutical composition comprises a hypochlorite solution as defined in any one of claims 1 to 18.
20. A method for improving the appearance of scar tissue, the method comprising administering an amount of a hypochlorite solution as defined in any one of claims 1 to 18 to a mammal, preferably a human, wherein the method is a cosmetic method and wherein the hypochlorite solution is administered topically.
21. A hypochlorite solution for use in the prevention or treatment of scar tissue in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt), optionally wherein the hypochlorite solution is as defined in any one or claims 1-18.
22. A hypochlorite solution for use according to claim 21, wherein the prevention or treatment of scar tissue is in the treatment of a wound.
23. A hypochlorite solution for use according to claim 21, wherein the prevention or treatment of scar tissue is in the prophylactic treatment of a lung disease or lung condition which causes scarring of the lungs.
24. A hypochlorite solution for use according to claim 21, wherein the prevention or treatment of scar tissue is in the treatment of purpura fulminans.
25. A hypochlorite solution for use in the treatment of purpura fulminans in a mammal, preferably a human, wherein the hypochlorite solution comprises hypochlorite in a concentration range of about 0.01-0.2 wt% (about 100-2000 ppm by wt).