Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
  • A61K8/20—Halogens; Compounds thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/08—Solutions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/06—Antipsoriatics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/08—Antiseborrheics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/04—Centrally acting analgesics, e.g. opioids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/005—Preparations for sensitive skin

Definitions

• the present invention concerns a new approach to the prevention and treatment of inflammation in a mammal, especially a human, e.g., in the 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, such as in leg ulcers or other venous ulcers, or in the prevention or treatment of an inflammatory skin condition such as mouth ulcers, eczema or psoriasis.
• oedema is a product of inflammation, which originates at the surgical site, in part, as a result of the cytokine response to surgical injury.
• the oedema and inflammation is associated with clinical outcome, morbidity and mortality, such that a reduction in post-surgical inflammation and oedema would result in improved outcomes (Vaughan-Shaw et al., Ann. R. Coll. Surg. Eng., 2013, 95:390-396).
• death was more likely in those with post-operative oedema (47% vs 8%).
• a dental extraction/oral surgical procedure is analogous to the intentional creation of a compound fracture in the oral cavity, where the wound is left to heal by secondary intention.
• osteomyelitis infection
• AO alveolar osteitis
• the incidence of AO following dental-oral surgical procedures is reported to be within the range of 5-40% (recent reports are consistently in the 22-30% range). This is similar to rates of delayed, difficult or painful healing reported for other surgical sites.
• Venous ulcers are chronic wounds and inflammatory lesions, which often require lengthy treatment periods to heal or are difficult to heal at all. Venous ulcers are estimated to affect approximately one million people per year in Europe, and half a million people per year in the USA. The condition is particularly prevalent in older people, with the UK National Health Service estimating that 1 in 50 people over the age of 80 develop venous leg ulcers. The economic impact of hard to heal ulcers has been provided by Rippon et al., Wounds , UK, 2007, 3(2):58-69. Current recommended treatments are compression treatment or simple wound dressing, but there remains a need for a cheap, effective treatment, which can aid the healing of non-healing or difficult to heal leg ulcers.
• the present gold standard for the treatment with irrigation or cleansing of wounds is sterile saline or sterile water, usually in conjunction with antibiotics for the routine treatment of non-infected wounds.
• Pre-operative site preparations are used as topical antimicrobial agents before surgery.
• the use of antiseptics is not recommended in this context (Atiyeh et al., Int. Wound J. 2009, 6: 420-430; Fournel et al., Brit. J. Surg., 2010; Brolmann et al., Brit. J. Surg., 2012, 99:1172-1183; Leaper, Br. J. Surg., 2010, 97:1601-1602; Walter et al., Brit. J. Surg., 2012, 99:1185-1194).
• aqueous chlorine solutions As anti-microbial and disinfectant agents, it is generally as a low pH solution to maximise the levels of hypochlorous acid, which is known to be an effective anti-microbial (see, for example, Chang, Journal of American Water Works Association, 1944, 36:1192-1207).
• hypochlorous acid which is known to be an effective anti-microbial
• pH of the aqueous chlorine solution is not deliberately kept low, such formulations use a buffer to maintain a higher pH and maximise stability of the solution (see, for example, Estrela et al., J. Appl. Oral Sci., 2008, 16(6):364-368).
• NVC-422 N-Chloramine compound
• the inventor of the present invention has now surprisingly found that that the aqueous hypochlorite solution according to the present invention is very beneficial in reducing the healing time and reducing the associated problems found with the healing of non-infected and uncontaminated surgical sites.
• aqueous hypochlorite solution of the present invention brings about the resolution of inflammatory disorders of the skin, mucosa and other surfaces, e.g., mouth ulcers, eczema, psoriasis, and leg ulcers, such as venous leg ulcers, where the cause is not microbial or infection.
• a specific hypochlorite solution has a novel action on the inflammatory response and healing process associated with uncontaminated and non-infected surgical sites and wounds, as well as trauma sites and surface inflammatory lesions where there is no infection, e.g., recurrent oral ulcers, allergic dermatitis/eczema, psoriasis, and leg ulcers, such as venous leg ulcers.
• a dilute stabilised hypochlorite solution for use the prevention or treatment of an inflammatory response, condition or disease in a mammal, preferably a human.
• a concentrated stabilised sodium hypochlorite solution to be diluted before use in the prevention or treatment of an inflammatory response, condition or disease in a mammal, preferably a human.
• the skilled practitioner is provided with the concentrated solution of the invention together with directions to dilute said solution to an appropriate concentration for the desired anti-inflammatory use.
• This concentration will either be known for a given condition or patient (based on prior knowledge of the condition and/or patient) or can be readily determined by simple trial and error by the practitioner of ordinary skill.
• a method for preventing or treating an inflammatory response, condition or disease in a mammal comprising administering an effective amount of a dilute stabilised hypochlorite solution to said mammal in need thereof.
• said mammal is a human.
• a dilute stabilised hypochlorite solution in the preparation of a medicament for preventing or treating an inflammatory response, condition or disease in a mammal.
• the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease is preferably dilute stabilised sodium hypochlorite solution. More preferably, said dilute stabilised sodium hypochlorite solution is in a concentration range of 0.005-0.2 wt %, yet more preferably 0.05-0.1 wt %.
• the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease may further comprise sodium chloride, preferably in a concentration range of 0.5-1.5 wt %, more preferably in a concentration range of 0.8-1.0 wt %.
• the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease may be a dilute stabilised sodium hypochlorite solution, which is buffered to a pH of from 5-11, preferably 6-8.
• the buffer may be any suitable buffer conventionally used in the pharmaceutical field, and is preferably selected from the group consisting of a phosphate/phosphoric acid buffer, a borate/boric acid buffer, and a citrate/citric acid buffer.
• the dilute stabilised hypochlorite solution of the present invention may be used in the prevention or treatment of an inflammatory response in an uncontaminated or non-infected surgical site, wounds, trauma sites or surface inflammatory lesions where there is no infection, preferably a non-healing wound or an oral wound.
• Infection in the context of the present invention has its ordinary meaning as would be understood by the person of ordinary skill in this field, e.g., the invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are not normally present within the body or at the site of the infection. Infection in this context can be either primary or opportunistic.
• the dilute stabilised hypochlorite solution of the present invention may also be used in the prevention or treatment surface inflammatory lesions, an inflammatory skin condition where there is no infection, and also in the treatment of inflammatory pain, rheumatoid diseases and Alzheimer's degenerative disorders of the nervous system e.g., mouth ulcers, eczema, psoriasis, leg ulcers, venous ulcers, venous leg ulcers, allergic dermatitis, contact inflammatory dermatitis, stasis dermatitis, seborrheic dermatitis, inflammatory nociceptive pain, inflammatory neuropathic pain, inflammatory stomatitis, rheumatoid arthritis, Alzheimer's disease, rosacea or lupus, preferably eczema, psoriasis, leg ulcers, venous ulcers or venous leg ulcers.
• inflammatory pain rheumatoid diseases and Alzheimer's degenerative disorders of the nervous system
• Eczema is an itching (pruritic) inflammatory condition of the skin, which can occur in response to known irritants, allergens or stresses.
• the cellular and histological changes associated with its pathology have been studied extensively.
• a typical sequence of inflammatory changes occurs at the site of inflammation, and the pathogenesis includes cellular action (e.g., mast cell degeneration) and release of inflammatory mediators (e.g., histamine and cytokines).
• Psoriasis is an immune-mediated disease that affects the skin. It is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Psoriasis occurs when the immune system mistakes a normal skin cell for a pathogen, and sends out faulty signals that cause overproduction of new skin cells. The cause of psoriasis is not fully understood. There are two main hypotheses about the process that occurs in the development of the disease. The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The problem is simply seen as a fault of the epidermis and its keratinocytes.
• T cells which normally help protect the body against infection
• cytokines tumor necrosis factor-alpha TNF ⁇ , in particular
• TNF ⁇ tumor necrosis factor-alpha TNF ⁇
• Leg ulcers are long lasting, chronic wounds and inflammatory lesions on the leg or foot. Venous leg ulcers are the most common kind of leg ulcer, and are particularly prevalent in older people. There are various causes of leg ulcers, but risk factors include obesity, deep vein thrombosis, varicose veins, diabetes, peripheral arterial disease and simply increasing age. Treatment includes compression treatment, such as by application of a compression bandage or graduated elastic medical compression stocking, and by simple dressing of the wound. Both require frequent monitoring and prolonged treatment periods, and can be ineffective in the treatment of hard to heal or chronic ulcers.
• the dilute stabilised hypochlorite solution of the present invention acts on the known initiators, mediators and regulators of inflammation in surgical sites and surface inflammatory lesions.
• 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.
• the dilute stabilised hypochlorite solution has a beneficial effect within specific concentration ranges, the exact identity of which will vary from condition to condition and patient to patient. These ranges are either disclosed in the present application or will be easily determined by the practitioner of ordinary skill in this field by simple trial and error on the basis of the knowledge of the present invention herein and the condition that is being presented.
• Beneficial effects for the prevention or treatment of an inflammatory response in an uncontaminated or non-infected surgical site, wounds, burns, trauma sites and for inflammatory skin conditions are particularly noticeable where the patient is treated with a dilute stabilised solution which has a concentration range of 0.005-0.2 wt %, preferably 0.05-0.1 wt %, more preferably 0.005-0.1 wt. % sodium hypochlorite; sodium chloride in a concentration range of 0.5-1.5 wt %, preferably in a concentration range of 0.8-1.0 wt %; wherein said solution is buffered to a pH of from 5-10, preferably 6-8.
• a dilute stabilised solution comprising 0.85% sodium chloride and 0.05% sodium hypochlorite w/w has been found to be very beneficial in preventing and treating an inflammatory response, condition or disease in a mammal, preferably a human, e.g., in uncontaminated or non-infected surgical sites, wounds, trauma sites or surface inflammatory lesions where there is no infection and in prevention and treatment of inflammatory skin conditions.
• This range of concentrations has previously been considered in the medical literature to be toxic.
• the hypochlorite should be very pure, e.g., ideally it should be generated electrolytically to ensure its purity as well as its safety and effectiveness.
• the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease according to the present invention may further comprise an indicator to show the activity of the dilute hypochlorite solution, in other words, the indicator shows the dilute hypochlorite solution is fresh and active.
• the indicator is not the active ingredient of the dilute hypochlorite solution.
• the indicator preferably degrades over time when mixed with the dilute hypochlorite solution. In other words, the indicator preferably does not degrade over time when mixed with either neat dilutant or neat hypochlorite.
• the indicator may comprise a first component which shows the dilute hypochlorite solution is fresh and active and a second component which degrades the first component.
• the indicator (e.g., first component) may be a dye or a flavour or combination thereof (e.g., in a mouthwash).
• the indicator preferably produces a noticeable change over time to a user of the dilute hypochlorite solution.
• a dye there is either a significant colour change or the solution becomes colourless.
• a flavour there is a noticeable degradation of the flavouring such that the solution becomes unpalatable. Since the resultant solution is most effective, if diluted immediately prior to use, the noticeable change may occur within a time frame of 45 minutes to 1 hour. In this time frame, the noticeable change occurs prior to the loss of therapeutic action of dilute hypochlorite solution.
• the dye may be a dye such as those which are routinely used in surgical procedures with no adverse effects.
• suitable dyes include azafloxin, basic blue (nil blue sulphate), bismarck brown, basic red (rhodamine 60), bengal red, brilliant crysyl blue, eosin, fluorescein, gentian violet, indocyanine green, Janus green, methylene green, methylene blue, neutral red, trypan blue, and trypan red.
• the predetermined amount of dye is preferably low enough to prevent interaction with active components but great enough so that the dye colour is visible within the dilute hypochlorite solution.
• the indicator may be organic or inorganic, biocompatible, non-toxic and pharmaceutically acceptable.
• the indicator (preferably a dye) may indicate the strength or dilution of the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease.
• the indicator dye may be blue.
• the hypochlorite is diluted by 20 (1 part of hypochlorite in 20 parts of water) the indicator would be green.
• the hypochlorite is diluted by 30 (1 part hypochlorite in 30 parts of water) then the hypochlorite dye would be orange.
• the hypochlorite is diluted by 40 (1 part hypochlorite in 40 of water) then the indicator dye would be red.
• the hypochlorite dye may preferably be packaged with the specific dilution.
• the indicator may also show that the hypochlorite for use in the prevention or treatment of an inflammatory response, condition or disease is at the correct dilution.
• the indicator may be an organic or inorganic dye which can be degraded by the innate oxidative capacity chemical action of the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease.
• the indicator may suffer a diminishment of intensity over a period of 1 hour. This indicates the activity of the dilute stabilised hypochlorite solution is not sufficiently reliable to produce the clinical action desired.
• the indicator is selected so that it degrades and shows a change in property over the same period in which the activity of the chosen dilution of the stabilised hypochlorite degrades. For example, one dye might change from coloured to colourless over 30 minutes, while another might make this change over 1 hour while another might take 2 hours.
• the colour degradation of the indicator dye may be used as an indicator of the reduction in activity of the dilute stabilised hypochlorite solution.
• the intensity of the colour can be measured by comparison to a set colour charts or with a calibrated optical measuring device to indicate hypochlorite activity.
• the dilute hypochlorite solution can have an indicator such as a dye added after its dilution to indicate continued activity.
• an indicator such as a dye added after its dilution to indicate continued activity.
• the dilute hypochlorite e.g., Milton's 2 wt % sodium hypochlorite or Milton's 1 wt % sodium hypochlorite in 16.5 wt % sodium chloride solution diluted with water
• the indicator may be an indicator dye which is an unstable compound which spontaneously degrades over a period of time (preferably from 30 minutes to 2 hours, e.g., over 30 minutes, 45 minutes, 1 hour or 2 hours).
• the indicator is preferably formed at the time of dilution of the disinfectant by adding two separate components together in order to generate the indicator dye. Once generated it is then added to the dilute hypochlorite solution, after which the indicator dye “degrades” from exhibiting colour (e.g., red, blue or green) to being colourless.
• a further advantage is that the dilute stabilised hypochlorite solution can be seen to be present at the treatment site. It can therefore be visually confirmed that the dilute hypochlorite solution is being delivered to the intended area and that it is being applied or circulated throughout the entire treatment site. Thus a blockage or incomplete circulation can be detected and the dilute hypochlorite solution can be reapplied as necessary.
• the inflammatory response, condition or disease is an ulcer, particularly a venous ulcer, e.g., a venous leg ulcer.
• the concentrated hypochlorite solution to be diluted before use is a concentrated stabilised sodium hypochlorite solution.
• the concentrated stabilised hypochlorite solution when diluted to the appropriate dilution to give a dilute stabilised hypochlorite solution may be used in the prevention or treatment of an inflammatory response, condition or disease in a mammal, preferably a human.
• the concentration of hypochlorite for use in accordance with the second aspect of the present invention may be in the range of 0.5 to 3 wt %. Furthermore, the concentrated hypochlorite solution may be buffered to a pH of from 9-15, preferably 11-13.
• 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 dilute 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 said solution is typically at a concentration of 16.5%.
• the ratio by volume of the hypochlorite solution to water may be in the range of between 1 to 10 to 1 to 40.
• 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.
• the ratio by volume of the hypochlorite solution to water may be in the range of between 1 to 5 to 1 to 20.
• 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 0.025%-0.2%, preferably 0.05%-0.1%.
• the action of the sodium hypochlorite solution can provide stabilisation of the dilute disinfectant solution.
• a method for preventing or treating an inflammatory response, condition or disease in a mammal comprising administering an effective amount of a dilute stabilised hypochlorite solution to said mammal in need thereof.
• said mammal is a human.
• the inflammatory responses, conditions or diseases, which may be treated and the dilute hypochlorite solutions suitable are as discussed and exemplified earlier in relation to the first aspect of the invention.
• the dilute stabilised hypochlorite solution may be administered for use as an irrigating solution for surgical sites, burns or wounds.
• Alternatives include:
• hypochlorite solution for inflammatory skin conditions, means for the constant application of hypochlorite solution to the affected area may be applied.
• hypochlorite solution for inflammatory skin conditions, means for the constant application of hypochlorite solution to the affected area may be applied.
• a dilute stabilised hypochlorite solution in the preparation of a medicament for preventing or treating an inflammatory response, condition or disease in a mammal, preferably a human.
• the dilute stabilised hypochlorite solution for use in the prevention or treatment of an inflammatory response, condition or disease in a mammal, preferably a human according to the present invention is preferably freshly prepared and administered, wherein said dilute stabilised hypochlorite solution is administered using a portable device for mixing a dilute hypochlorite solution comprising:
• the concentration of the hypochlorite solution in the disinfectant reservoir may be from 0.5 to 3 wt %, preferably 1 wt % or 2 wt %.
• the portable device for mixing a dilute hypochlorite solution may be in the form of a drip bag or a bottle.
• the portable device may be configured to deliver the dilute disinfectant solution to wounds.
• the chamber of the portable device is attached around the wound to retain the dilute disinfectant solution over the wound.
• a device suitable for preparing a dilute stabilised hypochlorite solution for use in the present invention is described in WO-A-2011/128862.
• a Caucasian north European male in 5 th decade has suffered atopic eczema since childhood.
• the patient presented with long-standing, chronic skin lesions on the anterior skin surface of the lower leg on the right and left side.
• the lesions had been present for 24 months and had proven refractory to treatment with topical hydrocortisone (1%) and emollient cream, with the lesions recurring despite temporary resolution.
• Treatment comprised application of a combination of the application of dilute stabilised aqueous sodium hypochlorite solution in saline (NaOCl: 0.05 wt %, NaCl: 0.85 wt %; pH 10) to the surface of the lesion alternating with the use of a gold standard emollient (DiprobaseTM, a cream comprising a mixture of liquid paraffin, white soft paraffin, cetomacrogol and cetostearyl alcohol).
• DiprobaseTM a cream comprising a mixture of liquid paraffin, white soft paraffin, cetomacrogol and cetostearyl alcohol.
• a paper square solution soaked in the dilute stabilised aqueous sodium hypochlorite solution in saline was applied against the lesion on the left leg and held in place with a TubigripTM elastic bandage. To prevent drying, the solution was replenished six times a day and worn for a 12-24 hour period. For the following three days, the emollient was applied
• the lesions on the patient's right leg i.e., the original control lesions
• This Example demonstrates the anti-inflammatory action of the dilute stabilised aqueous sodium hypochlorite solution in saline where the lesion is not a surgical site with haemostasis and where there is no infection. It was compared to isotonic saline as a control with identical soaking and emollient use.
• Example 2 The same patient as in Example 1 developed a new and acute atopic eczema lesion on the dorsal surface of the right foot. The lesion developed over a period of 6 hours beginning with severe itching and formation of broken skin with exudate production.
• the lesion was treated immediately with dilute stabilised aqueous sodium hypochlorite solution in saline, by soaking a towel with the solution and holding it in place with a TubigripTM elastic bandage. Treatment continued as described in Example 1, with dilute stabilised aqueous sodium hypochlorite solution in saline and the DiprobaseTMemollient.
• Patient B Another patient (Patient B) was a white Caucasian male, in his 7 th decade. He was a long-standing eczema sufferer. He had several lesions, which to him were defined by the cycle of itch-scratch-bleed-scab. The eczema had been resistant to treatment over several decades.
• a simple paper towel was saturated with dilute, stabilised aqueous sodium hypochlorite solution (NaOCl: 0.05 wt %, NaCl: 0.85 wt %; pH 7-8) and applied to the area using a TubigripTM elastic bandage.
• the saturated towel was replaced every 3-4 hours.
• the left leg and foot was left untreated as a control.
• Radiotherapy produces an obliteration of small blood vessels (endarteritis obliterans) in the irradiated area.
• tissue in the irradiated area can break down spontaneously and wounds such as fistulas are very difficult to heal. Such wounds commonly persist for months or years.
• dilute stabilised sodium hypochlorite solution in an attempt to address this inflammatory reaction, we administered dilute stabilised sodium hypochlorite solution to the wound area. Treatment was conducted with dilute stabilised sodium hypochlorite solution in saline (NaOCl 0.05 wt %, NaCl 0.5 wt %, pH 7-8) by dripping of the solution into the wound area to soak it, and by laying gauzes soaked in the solution over the wound. Treatment was for 90 minutes, twice daily.
• the fistula had closed by the 19 th day of treatment, and was now a wound. Normal hair growth in the skin at the edges of the wound had commenced. After 39 days, edges of rapid re-epithelialisation and signs of islands of keratinising (white) epithelium were observed. After 67 days, the skin wound was dry and could be managed simply with a dry dressing. After 102 days, the skin wound was almost completely healed.
• Dilute stabilised sodium hypochlorite solution in saline (NaOCl 0.05 wt %, NaCl 0.5 wt %, pH 7-8) was used in the management of a homogeneous set of oral surgical procedures.
• the study group comprised 377 cases. Details of the individual patient, site and nature of the surgery, and the clinical outcomes were recorded.
• control group an identical homogeneous set of oral surgical procedures were performed where no solution was used.
• the control group comprised 107 cases.
• the study group and control group were each operated on by separate clinicians, who had similar levels training, experience and competence in performing the oral surgery procedures.
• Anaesthesia/analgesia was achieved via standard approaches using standard local anaesthetic solutions licensed in the UK.
• the dental extractions were carried out using standard techniques as described in oral surgery textbooks and were applied homogeneously throughout the study and control groups.
• Haemostasis was achieved via local pressure over the socket with cotton wool rolls and biting pressure. Occasionally 3-0 braided silk sutures were placed.
• the wound/socket was irrigated with dilute stabilised sodium hypochlorite solution in saline using 10-20 mL of the solution via a syringe and a blunt ended needle (endodontic irrigation needle).
• Dental cotton rolls were soaked in the same solution and the patient applied biting pressure onto the wound via the soaked cotton rolls. The patient was instructed to rinse four times a day with dilute stabilised sodium hypochlorite solution in saline for five to ten days. Compliance with mouth rinse use was not monitored. All of the study group were reviewed a week after the surgical procedure.
• a 90 year old patient suffering from Alzheimer's disease presented a leg ulcer which had not healed over a six month period despite trying conventional treatments of pressure bandages and anti-microbial dressings. Furthermore, the situation was complicated because she removed the dressings during the day having forgotten why they were placed there. The ulcer often bled due to an anticoagulant therapy (warfarin) that she was taking for atrial valve incompetence. The leg ulcer had relapsed after previously successful treatment, the resolution having been short lived.
• warfarin anticoagulant therapy
• the treatment of this example comprised washing the leg ulcer for 10 minutes with a freshly constituted solution of sodium hypochlorite in saline (NaOCl: 0.05 wt %, NaCl: 0.85 wt %; pH 7-8) at twice daily dressing changes.
• the dressing itself was placed with a gauze square soaked with the same freshly constituted solution of sodium hypochlorite in saline.
• the washing and re-dressing was repeated twice daily and checked weekly for progress. It was found that the size of the ulcerated area diminished over the first 7 to 10 days and the surrounding inflamed and erythematous area was also reduced. Over a period of 3 weeks, the lesion diminished from its original dimension to less than 10% of its original surface area. Over the next 3 weeks it fully resolved and it has not recurred in the 18 months since.
• the dilute stable hypochlorite solution of the present invention provides a local anti-inflammatory agent which is an effective agent in treating this disorder. Furthermore, the treatment is simple, relying only on freshly constituted dilute sodium hypochlorite in saline used both as a wash and applied to the lesion via, for example, a soaked gauze.

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• 2014
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