Drug product and related methods

Abstract

A pharmaceutical composition for use as an active ingredient of a medicament or for use as an active ingredient in therapy comprising: (i) at least one milligram of iodide (I-); (iii) any one or more

Description

The present invention generally relates to a pharmaceutical composition or formulation for use as a medicament or in therapy, and related kits and methods, particularly but not exclusively suitable for use as a medicament or in therapy against multi-drug-resistant pathogens. The invention relates more particularly to: a pharmaceutical composition or formulation comprising iodide (I-) and an ascorbic moiety such as ascorbic acid; a pharmaceutical composition or formulation comprising iodide (I-) obtained from iodine (I2) or a suitable iodide precursor using a pharmaceutically acceptable agent; a kit, container or syringe of the pharmaceutical composition or formulation; a method of manufacturing the pharmaceutical composition or formulation; a method of preparing a medicament comprising the pharmaceutical composition or formulation; use of ascorbic acid / ascorbate or another pharmaceutically acceptable agent to generate iodide (I-) from iodine (I2) or a suitable iodide precursor; a method of preparing / protecting an organ or tissue or bodily fluid ex vivo using the composition / formulation; and a container including the organ / tissue / bodily fluid treated using the composition / formulation. BACKGROUND TO THE INVENTION Historically, infectious diseases were sometimes treated by herbal remedies or other traditional medicines, but recovery was to a large extent determined by whether a person’s own immune system could overcome the disease. Following the discovery and later widespread availability of antibiotics, along with vaccines and improved sanitation, global deaths due to common infectious diseases became significantly reduced. At present there are well over 100 antibiotics, but the majority come from only a few types of drugs. Most antibiotics have two names, the trade or brand name created by the drug company that manufactures the drug, and a generic name based on the antibiotic's chemical structure or chemical class. Each antibiotic is effective only for certain types of infections. The main classes of antibiotics include: Penicillins such as penicillin and amoxicillin; Cephalosporins such as cephalexin (Keflex (RTM)); Macrolides such as erythromycin (E-Mycin), clarithromycin (Biaxin), and azithromycin (Zithromax (RTM)); Fluoroquinolones such as ciprofolxacin (Cipro), levofloxacin (Levaquin (RTM)), and ofloxacin (Floxin); Sulfonamides such as co-trimoxazole (Bactrim) and trimethoprim (Proloprim); Tetracyclines such as tetracycline (Sumycin, Panmycin) and doxycycline (Vibramycin (RTM)); Aminoglycosides such as gentamicin (Garamycin) and tobramycin (Tobrex (RTM)). Unfortunately, due to widespread improper use of antibiotics globally, some pathogens have evolved and developed resistance to antibiotic drugs, in some cases resulting in multi-drug resistant (MDR) pathogens which are colloquially known as ‘superbugs’. The top ten generic antibiotics include: Amoxicillin, Doxycycline, Ciprofloxacin, Clindamycin, Metronidazole, Azithromycin, Sulfamethoxazole and Trimethoprim, Amoxicillin and Clavulanate and Levofloxacin. All of these antiobiotics have documented cases of microbial resistance, apart from Clavulanate which is always used in conjunction with penicillin-based antibiotics. Drug resistance develops over time when microbes are exposed to antibiotics or anything with a mechanism that inhibits the replication cycle of the infectious pathogen. Whilst different combinations of antibiotics have had some success in dealing with superbugs, it is only a matter of time until those pathogens evolve further. The World Health Organization (WHO) has declared that antimicrobial resistance is one of the top ten global public health threats facing humanity. Infectious disease can be caused by various pathogens, including various bacteria, viruses and fungi. Bacterial, fungal and viral infectious microbes are, and will continue to be, a constant threat to human health. There will always be opportunistic, zoonotic and emerging infectious pathogens. The eight bacterial, four fungal and two viral pathogens outlined below are becoming of great concern and pose an increasing risk to human health worldwide. In terms of bacterial infections, the following are of particular concern: Staphylococcus aureus, Methicillin-resistant staphylococcus aureus (MRSA) and Vancomycin-intermediate and resistant staphylococcus aureus (VISA) and (VRSA), in addition to the others discussed below. More than 3 million people in the US carry Methicillin-resistant staphylococcus aureus (MRSA) on their skin. When this develops into a colonised infection the risk of mortality is substantially increased from 18% to 36%. MRSA is the most common cause of skin and soft tissue infections in the US, with 5-10% of community-based infections being invasive and potentially life threatening. Staphylococcus aureus nasal carriage in the global population varies between 20-35%. Thus, colonised infections are easily acquired following skin trauma, as a secondary infection or when underlying medical conditions, such as immune deficiency, are present. Regarding Vancomycin Resistant Enterococci faecium (VRE), the Centre for Disease Control and Prevention (CDC) estimates that roughly 30% of all healthcare-associated enterococcal infections are resistant to vancomycin, with almost all VRE infections taking place within healthcare environments. VRE is becoming increasingly resistant to additional antibiotics currently used and therefore newly emerging multi-drug resistant enterococci species are of great concern. In the USA, it is projected that a patient with a VRE blood stream infection will, on average, have an increased length of hospital stay from 10.5 days to 46 days with an associated increase in cost of $27,190. With respect to Enterococcus hirae, Enterococci are Gram-positive facultative anaerobic cocci in short and medium chains, which cause difficult-to-treat infections in the nosocomial setting. Enterococci cause 15-20% of urinary tract infections (UTIs) in the hospital setting. They have intrinsic resistance to some antibiotics and are highly resilient to various antiseptics and disinfectants. Multi-drug resistant pseudomonas aeruginosa is also emerging as a prevalent nosocomial infection. A case-control surveillance study performed in China showed that the prevalence of MDR P. aeruginosa was 54% among patients with P. aeruginosa infections. Acinetobacter is a genus of aerobic, glucose non-fermentative, rod-shaped, coccobacilli, Gram-negative Gammaproteobacteria in the family Moraxellaceae of phylum Pseudomonadota. Carbapenem-Resistant Acinetobacter baumannii (CRAB) is a group of A. baumannii which have developed increased or complete resistance against many antibiotic agents, including carbapenems which are deemed as lastresort antibiotics. A. baumannii is classed as a nosocomial pathogen especially in intensive care and burn units causing pneumonia, bloodstream infections, skin structure infection and urinary tract infections. It has been identified by the WHO as a critical priority antibiotic-resistant pathogen. In the USA, Carbapenem-Resistant Acinetobacter baumannii is associated with increased mortality and hospital length of stay. In 2017, it was estimated by the CDC that 700 deaths occurred in hospital in America due to CRAB. Clostridioides difficile, formerly known as Clostridium difficile, is a bacterium that causes diarrhoea, intestinal infections and colitis. It employs multiple mechanisms to circumvent antimicrobials, such as endospore formation with Clostridium difficile, a significant, high risk, acquired nosocomial infection. The CDC estimated that nearly 223,900 people require hospital care for C. difficile and at least 12,800 people died in 2017 from C. difficile infections. C. difficile was classified as an urgent threat by the CDC Antibiotic Resistance Threats in the United States Report 2019. Enterobacterales are a large order of different types of bacteria that commonly cause nosocomial and community-based infections, which include Escherichia coli (E.coli) and Klebsiella pneumoniae. In 2017, there were an estimated 197,000 cases of Extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales among hospitalised patients and 9,100 estimated deaths in the US. Neisseria gonorrhoeae is a Gram-negative, diplococcus shaped bacterium that only colonizes humans. Infections start by attachment to epithelial cells in mucous membranes, especially in the reproductive tract, mouth, throat and eyes. Females with untreated infections that spread to the uterus and fallopian tubes can lead to infertility amongst other conditions. The WHO estimates that in 2020 there were 82.4 million [47.7 million-130.4 million] new cases infected among adolescents and adults aged 15-49 years old worldwide. As high as 30% of Gonorrhoea infections are reported to be antibiotic resistant, and MDR, with only one treatment option left globally. In 2020, a total of 677,769 cases of gonorrhoea were reported to the CDC, making it the second most common notifiable sexually transmitted infection in the United States for that year, with an increase in rates of 111% since 2009. Neisseria gonorrhoeae fluoroquinoloneresistant strains circulate worldwide and, in some areas, show 100% resistance to fluoroquinolone. Mycobacterium tuberculosis, from the family Mycobacteriaceae, is the causative agent of tuberculosis and is one of the top 10 causes of death worldwide. In 2020, an estimated 1.514 million deaths were TB-related. According to the WHO global tuberculosis (TB) report, an estimated 5.8 million new cases and 157,903 rifampicin (RIF) / multidrug-resistant (RR / MDR) TB cases were recorded in 2020. Mycobacterium Terrae is used in a laboratory setting as a surrogate for Mycobacterium tuberculosis because it has been shown to be slightly more resistant and as such is used to represent TB infections. In terms of fungal infections, the following are of particular concern: Candida albicans, Aspergillus fumigatus, Cryptococcus gattii, and Mucormycosis. Candida albicans is the most prevalent and most pathogenic of the Candida species and is responsible for the majority of oral and systemic candidiasis cases, as well as community-onset and nosocomial candidemia’s. Vulvovaginal candidiasis (thrush) affects up to 75% of women at least once in their lifetime. More recently Candida auris was identified in 2009 in Japan as a newly emerging multi-drug resistant fungal pathogen which has now spread globally. The disseminated forms of the candidiasis can be life-threatening with mortality rates of 35-60% among immunocompromised cancer patients and patients exposed to multiple treatments, such as broad-spectrum antibiotics, chemotherapy, immunosuppressive therapy, and antiretroviral therapy. Regarding Aspergillus fumigatus, invasive aspergillosis occurs mainly in immunocompromised people with a predicted case number of 1-2 cases per 100,000 population in America. Recent global estimates found 3 million cases of chronic pulmonary aspergillosis. It was found that the one-year survival for people who had invasive aspergillosis was 59% among solid organ transplant recipients and 25% among stem cell transplant recipients. In a systematic review of intensive care unit autopsy studies, aspergillosis was one of the top four most common diagnoses that likely lead to death. Cryptococcus gattii is a basidiomycetous yeast, which grows mainly as an asexual budding yeast. This fungus lives in primarily tropical and sub-tropical areas of the world and causes cryptococcosis disease, usually affecting the lungs and central nervous system. It is a major opportunistic infection and is the leading cause of death in adults living with HIV in sub-Saharan Africa. Cryptococcus gattii has, due to climate change, colonised new geographic locations over the past 20 years and is now a global concern. Mucormycosis is a serious angioinvasive fungal infection caused by a group of molds called mucormycetes (or Mucor). In people who are immunocompromised, these fungi replicate in the nasal passages, eyes, palate, brain and in rare cases the lungs. Mucormycosis is spread by spores through inhalation, contaminated food, or contamination of open wounds and are commonly found in soils, decomposing organic matter and animal faeces. Treatment is surgical debridement and less than 50% of those infected survive. The survivors generally suffer from serious facial disfigurement, blindness and / or loss of taste / smell / ability to masticate. Mucormycosis is fatal in almost all cases where it infects the lungs, stomach or brain. The prevalence of Mucormycosis in India was determined to be 0.14 per 1000 population, which is more than 80 times the prevalence in developed countries. In terms of viral infections, the following are of particular concern: influenza virus and human Coronavirus. Influenza is a contagious respiratory virus that infects the nose, throat and sometimes the lungs. It is spread by aerosolised droplets and touching infected surfaces. Influenza viruses that infect humans are classified as either Influenza A Influenza B or Influenza C and are from the viral family Orthomyxoviridae. According to the 2018 CDC published report on Clinical Infectious Diseases 8% of the U.S population contracts seasonal flu each year. H1N1 is an Alpha virus. Human coronavirus is an RNA virus from the family Coronaviridae, which is further subdivided into the Orthocoronavirinae subfamily. Within this subfamily there are four Genera: Alpha, Beta, Gamma and Delta. The common human strains 229E and NL63 are from the Alpha coronavirus Genus, but SARS-CoV-2 is from the Beta coronavirus Genus. Human coronavirus is also a contagious respiratory virus. According to the WHO, SARS-CoV-2 (the COVID-19 virus) case number now totals over 756,291,327 globally with over 6,841,640 deaths reported. Infectious diseases still infect and kill millions of people every year, and the numbers dying are increasing in part due to increasing levels of drug resistance in pathogens. It is estimated that over 700,000 deaths each year are caused by multi-drug resistant (MDR) bacterial infections. In America alone, the Food and Drug Administration (FDA) has documented 2.8 million antibiotic-resistant infections per year, with over 23,000 people dying as a result. Globally over 300 million people are afflicted with serious fungal infections, with more than 1.5 million of those people dying each year as a result. In additional to societal and personal costs of disease, the financial costs are substantial. In America, the financial costs related to the top five healthcare-associated infections are counted in billions of US dollars, with surgical site infections dominating. Moreover, the few remaining antibiotics that can be used against resistant strains of microbials are exponentially increasing in value due to increasing global demand. The average US price for branded antibiotics for treatment of a single indication in 2022 was $221. A comprehensive global report estimated that 4.95 million deaths were associated with bacterial antimicrobial resistance (AMR) in 2019, including 1.27 million deaths attributable to bacterial AMR. The six identified leading pathogens for deaths associated with resistance were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. These six bacteria were collectively responsible for 929,000 deaths and attributable to 3.57 million deaths associated with AMR in 2019. One pathogen-drug combination, methicillin-resistant S. aureus, caused more than 100,000 deaths in 2019. Also in 2019, the Centre for Disease Control and Prevention (CDC) in the USA reported that more than 3 million infections per year are caused by antibiotic-resistant infectious pathogens. More than 70% of nosocomial infections are resistant to at least one of the antibiotics commonly used to treat them. According to Public Health England in the United Kingdom, there are 178 new antibiotic-resistant infections diagnosed each day, not discounting all of the non-resistant infections that commonly circulate in society. With ever-increasing levels of antimicrobial resistance developing globally, it is difficult for a clinician to know which pathogen is causing an infection or if that pathogen is resistant to the standard antibiotic therapy without laboratory analysis. It is becoming increasingly common for patients to present with certain antibiotic-resistant infections, which leads to multiple dosing with antibiotics that are not effective. This process can continue for weeks or even months before the correct antibiotic is prescribed. During which time the infection can progress from mild to severe and contribute to the development of AMR. Two examples of bacterial antibiotic resistance which have been highlighted as causes for concern by the WHO are (MDR) Neisseria gonorrhoeae and Enterobacteriaceae. Since the 1960s, antibiotics have been used to treat Neisseria gonorrhoeae infections and antibiotic resistance has since developed. According to the CDC, resistance to Penicillins and Tetracyclines emerged in the 1980s, followed by resistance to Fluoroquinolones in the 1990s. As of 2007, global fluoroquinolone resistance to Neisseria gonorrhoeae was documented. Today, only one antibiotic type, Cephalosporins, are effective against Neisseria gonorrhoeae and this is also starting to show cases of resistance. Multi-drug resistant Enterobacteriaceae represent bacterial species such as Escherichia coli, and Klebsiella pneumoniae. Over time, through horizontal gene transfer, Escherichia coli has developed resistance to cephalosporins, carbapenems, aminoglycosides and most recently to fluoroquinolones and polymyxins. Klebsiella pneumoniae has also shown emergence of hypervirulent strains and developed resistance to carbapenems and polymyxin E, an antibiotic used as a last-resort treatment for multidrug-resistant gram-negative bacterial infections. In addition to known and well-established pathogens, the world is facing the emergence and spread of many new pathogens, in part due to factors such as climate change and zoonosis. It is unknown whether existing antibiotics and other drugs will prove effective in treating new pathogens. Furthermore, most new drugs brought to market now have a very targeted and specific mode of action and so cannot be used to treat infections caused by different organisms. Whilst this can be advantageous to limit the risk of drug resistance developing in nontarget organisms, infections that become resistant to conventional treatment or do not currently have any specific treatment options can become life-threatening very quickly. More common infectious diseases are often the subject of comparatively greater research than rarer diseases, in part because treating or curing a common disease is considered to have a greater or more widespread benefit. On the other hand, rarer diseases can take longer to diagnose and effective treatments have not always been developed due to the cost of pharmaceutical research and development and considerations regarding potential return on investment. For example, it has been shown that 28% of rare disease patients can wait more than 7 years in the USA and more than 5 years in the UK for an accurate diagnosis. Every day, Hospital Acquired Infections (HAIs) result in prolonged hospital stays, long-term disability, increased resistance of microorganisms to antimicrobials, substantial additional costs for health systems, high costs for patients and their family, and unnecessary deaths. The clinical ‘pipeline’ of new antimicrobial and antibiotic drugs is running dry and there is a substantial risk that some infections will no longer be treatable by any existing antibiotics or antimicrobials in the near future. There is a global need for new pharmaceutical drugs to treat people who are infected by drug-resistant pathogens, particularly but not exclusively the pathogens mentioned above. Furthermore, humans are not the only species at risk of existing and emerging pathogens. Various epidemics have affected both wild animals and livestock over recent years. In particular, foot and mouth, bird flu and swine flu (amongst others) have caused many animal deaths and have indirectly led to the need to cull thousands or millions of animals in an attempt to control the spread of disease in animals and humans. The same is notable for tuberculosis in badgers, for example, where regular culling can be undertaken. Whilst such drastic action can reduce or halt the spread of disease, it is not guaranteed to do so and in any case involves an incredible loss of animal life. It is an object of the present invention to reduce or substantially obviate the aforementioned problems. STATEMENT OF INVENTION In any of its aspects, the invention may be considered as a broad-spectrum drug product. It is proposed for prescription to a patient as a first response or therapy (i.e. a first-choice drug) to an infection, without fear of microbial resistance developing. This is expected to resolve many infections and reduce the length of treatment required, saving patient and insurer money, and saving clinician time, and also saving governments and non-governmental organisations (NGOs) time and effort in existing and emerging health threats from micro-organisms. Whilst the patient is generally expected to be a human, it is envisaged that compositions or formulations according to the invention may in some cases be used for an animal (particularly but not exclusively a mammal). In some examples, the invention may be used in the treatment of rare, resistant and / or recurring infectious diseases. In some examples, the invention may be used to automatically treat ‘at risk’ close contacts of any patient(s) presenting with a transmissible infection or a sexually transmitted infection (for example Neisseria gonorrhoeae, due to the extensive antimicrobial resistance (AMR) elicited by that pathogen). Throughout this specification, the term ‘PN13’ may be used to refer to the present invention, particularly a composition / formulation of the invention. The active ingredient of the invention may be considered to be iodide (I-) or the combination or iodide (I-) and an ascorbic moiety. Based on the current literature, no link has been observed between the active found in PN13 and the development of microbial resistance or evasion. Indeed, resistance to iodide (I-) - considered to be the active ingredient in PN13 - has not been observed over the past 100 years or so of documented use. I'can elicit microbicidal activity through strong oxidizing effects on the amino (HN_), thiol (HS‘) and phenolic hydroxyl (HO-) groups of amino acids and nucleotides. It can also interact with the fatty acids in the cell wall and cell organelle membranes, inducing pore formation resulting in cytosol loss. Anti-biofilm activity has also been demonstrated against Staphylococcus aureus. Furthermore, biofilms of antibiotic resistant bacteria Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and MDR Candida albicans, Candida auris and the fungus Aspergillus fumigatuswere shown to be eliminated following I’ administration. The virucidal effects of I’ were shown to cause DNA fragmentation and DNA strand breakage following in vitro infection with Influenza A virus. Iodide ions are an essential dietary mineral which are also known to be a high affinity substrate for the heme (or haem) enzyme myeloperoxidase (MPO) which is involved in bacterial cell killing during the immune response. It is also proposed that I; acting as a substrate, can protect against cell and tissue damage during inflammation. According to a first aspect of the present invention, there is provided a pharmaceutical composition or formulation comprising iodide (I-) and an ascorbic moiety for use as a medicament or as part of a medicament or in therapy. According to a second aspect of the present invention, there is provided a pharmaceutical composition or formulation comprising iodide (I-) obtained by reduction or reaction of iodine (I2) (and / or another suitable iodide precursor) in the pharmaceutical composition or formulation for use as a medicament or as part of a medicament or in therapy. The reduction or reaction is preferably effected by a pharmaceutically-acceptable agent. Throughout the applicant’s in vitro pre-clinical investigations, the invention demonstrated rapid and potent inactivation against commonly acquired nosocomial drug resistant infections as well as community-transmitted fungal, bacterial, and viral pathogens. This included many pathogens highlighted as causes for concern by the WHO. The active ingredient has a short half-life in the human or animal body. That is, a short biological half-life. The drug is also non-toxic and is well-tolerated in large and / or repeated dosage rates. The drug has a broad microbial target range against which it is effective. It is suitable for short term and repeated use. It is suitable for treating multiple different infections which present rapidly and require immediate medical intervention. The invention has potential for mass prescription use globally. The invention has been shown to be safe and stable during pre-clinical evaluation and, based on the current literature, the development of microbial resistance or evasion has not been documented in response to exposure to the active in the present invention. This underlines the great potential of the invention as a general use antimicrobial, or as a first-choice medicine. This will enable reduced reliance on conventional antibiotics, which may consequently reduce the rate of emerging antibacterial, antifungal and (to a lesser degree) antiviral resistance seen globally. The invention can be used for multiple indications against resistant and / or non-resistant strains and the treatment of these indications may be repetitive. For the avoidance of doubt, the Applicant expressly considers that any aspect of the present invention may apply or be used for any indication or medical purpose, whether for treatment or therapy or prophylaxis or otherwise. Due to the broad spectrum killing and inactivation targets elicited by the active ingredient in the present invention, it is believed that resistance doesn’t have time to develop against the multiple mechanisms employed, such as retardation of bacterial protein synthesis, disruption of electron transport, DNA denaturation or membrane destabilization. Thus, the infectious pathogen is not able to replicate upon exposure to the active ingredient and so it is believed that a chromosomal change cannot occur, thus preventing any resistance from passing to subsequent generations of the pathogen. There are various mechanisms of action which can simultaneously interfere with essential steps in bacterial, fungal or viral reproduction I lifecycles, including: oxidative damage to proteins within the cytoplasm by penetrating the membrane channels (porins); retardation of bacterial protein synthesis; disruption of electron transport; DNA denaturation; membrane destabilization; inhibition of growth via oxidative stress; damage to amino groups; damage to double bonds; damage to sulfhydryl groups; inhibition of fungal biofilm formation; inhibition of bacterial biofilm formation; generation of hydroxyl radicals; oxidative promoting actions. To date, no reports have shown induction of horizontal gene transfer, development of resistance genes, cross-tolerance or cross-resistance to the active ingredient(s) in the present invention. There are synergistic advantages to the introduction of a new broad spectrum antimicrobial therapeutic option involving the present invention. It would benefit patients, healthcare professionals and healthcare insurers through improved diagnostic, treatment, discharge and recovery timelines, but also the pharmaceutical companies. This is anticipated because, by bringing to market a broad-spectrum antimicrobial to which infectious pathogens should not be able to acquire resistance, it should allow the pharmaceutical industry to concentrate on drug development for more specialist and bespoke therapies. In the present invention, in preferred embodiments where an ascorbic moiety is present and where iodine is used to generate iodide, the iodine is the oxidising agent and leads to oxidation of the ascorbic moiety whilst the iodine is itself reduced to iodide (an ionic species). The ascorbic moiety may in some preferred embodiments be ascorbic acid and / or sodium ascorbate. This is because these two moieties are currently listed as excipients which are acceptable to the FDA. Whilst iodine (I2) is preferred for generating iodide (I-), the option of using an ‘iodide precursor’ is intended to mean a compound or compounds which is / are suitable for generating / releasing iodide (I-), whether by means of reduction or by another means (for example, hydrolysis or substitution or displacement or cyclisation to release iodide). For example, an interhalogen compound such as ICI (iodine monochloride) and / or IBr (iodine monobromide) and / or an alkyl iodide such as any of an ethyl iodide, a propyl iodide or a butyl iodide (such as a diiodide or triiodide of any of these) may be a source of iodide (I-). The alkyl iodide may be linear or branched or cyclic, or have a combination of such features. More generally, iodised versions of any suitable organic compound (such as monoiodised, or poly-iodised, fatty acids or proteins or carbohydrates or glycoproteins or glycolipids) may be considered to be suitable as an iodide precursor. This is particularly applicable where loss of iodide (e.g. by reaction such as hydrolysis) results in a bio-acceptable form of whatever iodised organic compound(s) were provided. Depending on the required dosage and application, any of the iodide precursors noted above may be considered as a suitable alternative or addition to iodine in the composition / formulation. Preferably any iodide precursor should only react to form non-toxic products or biologically tolerable products (and, in either case, preferably metabolizable products) in addition to whatever iodide is made available. The pharmaceutical composition / formulation should contain a therapeutic amount of iodide. That is, an amount substantially higher than a recommended daily intake amount. The pharmaceutical composition / formulation may contain at least 1 milligram (mg) of iodide (I-). The pharmaceutical composition / formulation may contain at least some water and / or solvent (particularly a biologically tolerable solvent). The amount of water and / or solvent may be selected to facilitate the formation of iodide (I-) by reacting the iodine (or iodide precursor) with the relevant ascorbic moiety (or other pharmaceutically-acceptable agent). The minimum amount of water and / or solvent required to form iodide (preferably from reacting substantially all of the iodine and / or iodide precursor) may be provided, or an amount of water and / or solvent that is somewhat larger (perhaps up to 10 times larger) than the minimum amount may be provided. The pharmaceutically-acceptable agent may include an ascorbic moiety, particularly any one or more of the group comprising: an ascorbic acid, a dehydroascorbic acid or one or more other oxidation derivatives of ascorbic acid or a pharmaceutically acceptable salt (e.g. ascorbate or buffered ascorbic acid) of any of the group. The reduction of iodine (I2) (or the iodide precursor) may be in situ reduction which occurs in the pharmaceutical composition / formulation as part of its manufacture or as part of preparation of the active ingredient portion of the composition / formulation. The generation of iodide (I-) may occur ex vivo. The reaction / reduction of iodine (I2) (or the iodide precursor) may occur ex vivo. That is, prior to using the composition / formulation in the course of carrying out treatment or therapy. The reduction or reaction of iodine (or the iodide precursor) to generate iodide may be a complete reduction or complete reaction, meaning that substantially none of the iodine or precursor is leftover or remaining in the composition. In the case of the iodide precursor, complete reduction / reaction is only intended to mean the extent required to liberate all of the iodide / iodine intended for release from the precursor, and not to further react / reduce the resulting moiety. There may be substantially no iodine (I2) in the pharmaceutical composition / formulation. That is, there may be iodide (I-) but an absence of iodine in the pharmaceutical composition / formulation. There may be no aqueous iodine (l2(aq)) in the pharmaceutical composition / formulation. The composition or formulation may have a pH in the range substantially pH 1 to substantially pH 6. Preferably, the pH is in the range substantially pH 2 to substantially pH 5. These ranges are preferred for pHs for the point of use, i.e. where the composition / formulation is ready to administer to a patient. In preferred embodiments, the pH of the composition is up to about pH 5. For example, a pH in the range 2-3 may be preferred for intravenous injection. In another example, a pH in the range 4-5 may be preferred for subcutaneous / intradermal delivery. The composition or formulation may include a pH adjuster or pH-adjusting excipient. That is, a compound or compounds which are used to change the pH of the active ingredient portion or of the composition / formulation. This may be preferred for providing a biologically tolerable / suitable pH. That is, this may apply if the pH of the active ingredient or composition / formulation is too acidic or too alkaline for immediate use in / on a patient. The pH adjuster or pH-adjusting excipient may be a base. Preferably it is a base when it is charge-neutral, or not negatively charged. That is, it is preferably a base without having a discrete cation or without itself being an anion. The pH adjuster or pH-adjusting excipient may have one or more pairs of electrons (e.g. a lone pair or pairs) - on an atom of neutral electric charge within a given molecule - which are each available for protonation. If the pH of the active ingredient or composition / formulation is already biologically acceptable, then a pH adjuster may not be needed. The active ingredient may be provided separately to any pH adjuster or excipient and so on. A first (active ingredient) portion of the composition / formulation may have a pH for storage which is in the range substantially pH 1 to substantially pH 3. A second (pH adjuster / excipient) portion having a pH for storage which is in the range substantially pH 10 to substantially pH 12. The pH of the composition / formulation when first prepared from the two or more portions may be about pH 5. The pH of the composition / formulation after up to about 30 minutes after combining or mixing the two or more portions may be about pH 4 to 5, or about pH 4.5. In some preferred embodiments, the composition / formulation (or second portion thereof) may include diethanolamine. The diethanolamine (CAS:111-42-2) may be provided as a pH adjuster and / or as an excipient. Diethanolamine is preferred because it is understood to be a non-active excipient, as well as being a pH adjuster. The amount of diethanolamine required to effect the desired pH increase to the above ranges can also meet anticipated regulatory and safety requirements. Nonetheless, it will be appreciated that other pH adjusters may be used in some embodiments, whether an organic base or an inorganic base. For example, in some instances it may be appropriate to select any one or more of: carbonate (CAS 3812-32-6), bicarbonate (CAS 71-52-3)), sodium bicarbonate (see CAS 144-55-8), sodium hydrogencarbonate, potassium bicarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, tromethamine (such as THAM (CAS 77-86-1), optionally up to 0.12 w / v). On the other hand, either of the composition / formulation or the pH adjuster may substantially lack a metal cation or metal cations (subject to having H+ or another stabilising cation that is not metal such as quaternary ammonium (such as NH4+ or monoalkyl or polyalkyl ammonium, where alkyl is typically any of Ci-Ce alkyl)). For example, they may lack any one or more: Na+, K+, Mg2+, Ca2+, Fe2+, Fe3+, Cu+, Cu2+, Zn2+. In some examples, the pH adjuster may be selected to deliberately lack / exclude any of: sodium bicarbonate, sodium hydrogencarbonate, potassium bicarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide. More generally, the composition / formulation or pH adjuster may lack any metal cation (whether selected from the above list or not) that can preferentially form compounds with any iodide ions (I-) or displace H+ and / or water from association with I’ in solution (particularly aqueous solution). The reason for ideally minimising or excluding metal ions (e.g. sodium and / or potassium, or others mentioned above) is to maximise long term storage of the composition. In storage, if those elements were present and interacting with iodide, it is envisaged that sodium iodide or potassium iodide may gradually form, which may be via crystallisation. This would reduce the available free iodide in the pharmaceutical composition / formulation. Those two metal iodide compounds are not active ingredients of the pharmaceutical composition / formulation, unlike free iodide (in the sense meant in the present invention). It is also possible that the presence of sodium (or other metal) ions either pre- or post-pH-buffering may affect the oxidation process and any related colour change in the pharmaceutical composition / formulation that may occur during that step. The presence of sodium or potassium, or potentially other metal cations, is thus believed to potentially lead to reduced efficacy of the composition over time and so it is believed to be advantageous to avoid including them in some preferred embodiments of the invention. It should be appreciated that the invention may still include sodium or potassium moieties such as their ascorbates, for example, but there does not appear to any substantial advantage to doing so based on the Applicant’s research and development work. At least some of the iodide (I-) in the composition / formulation may be free iodide. Preferably most or substantially all of the iodide in the composition / formulation may be free iodide. The free iodide may be stable in the composition / formulation. That is, there are preferably few or no compounds which would react with or scavenge the iodide to lower the amount of free iodide. The term ‘free iodide’ is intended to mean iodide (I-) which is predominantly unassociated with a metal cation. Put another way, some or all of the iodide ions may have respective coordination spheres of solvent (e.g. water) molecules and / or other components of the composition / formulation, and the negative charge on each may be balanced or stabilised by corresponding protons (H+) in the composition, but there are preferably relatively few (if any) metal cations associated with the iodide. For example, sodium and / or potassium may not be present. Other examples of metal cations which may be absent are discussed above. The iodide in the composition / formulation may be aqueous iodide (l'(aq)). The iodide in the active ingredient portion may be aqueous iodide (l'(aq)). In either or both of the composition / formulation and the active ingredient portion, the following concentrations may be provided. The molar concentration of iodide (I-) (particularly aqueous iodide) may be up to about any of: 1.0, 0.90, 0.85, 0.80, 0.75, 0.70, 0.65, 0.60 or 0.55 mol dm-3. In some preferred embodiments, the molar concentration of iodide (I-) (particularly aqueous iodide) may be up to about any of: 0.5, 0.45, 0.40, 0.35, 0.30 or 0.25 mol dm-3. Preferably, the molar concentration of iodide (I-) (particularly aqueous iodide) is at least about 0.001 or 0.002 mol dm-3. The preferred concentration may depend on many factors, including delivery route, characteristics of the patient, and the condition / pathogen which may be the target of the treatment. In preferred embodiments, the molar concentration of iodide (I-) may generally be in the range 0.005 to 0.40 mol dm-3 (that is, prior to use in / on a patient). For example, the concentration of iodide for an infusion may be about 0.002, about 0.004 or about 0.01 mol dm-3. In another example, the concentration of iodide for an injection may be about 0.05 mol dm-3, about 0.10 mol dm-3 or about 0.25 mol dm-3. If the composition / formulation is injected into blood or plasma, for example, then the concentration after dilution in blood I plasma may be calculated. For example, in an average US male human having about 4 litres of plasma, an injection of composition / formulation comprising 0.465g of iodide, the diluted concentration of iodide may be about 0.12mg / ml (or 0.12 g / l) which is equivalent to about 0.000946 mol dm-3. If a doctor, nurse or other medical professional or carer for a patient needs to achieve a minimum iodide concentration in the patient’s plasma, then the amount of composition / formulation (and therefore iodide) can be calculated accordingly for that particular patient by scaling up or down according to their estimated blood or plasma volume. The amount of iodide may be substantially at least any of: 0.12, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55 or 0.6 mg / ml. The amount of iodide may be substantially up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175 or 200 mg / ml. A range of iodide concentrations may be provided having a lower limit, an upper limit, or both a lower limit and an upper limit independently selected from either or both of these preferred minimum and maximum iodide amounts. The volume of composition / formulation may be between about 1ml to 50ml. In some cases (e.g. for topical application to a relatively small wound, or perhaps subcutaneous / intramuscular application), a small amount of2-3ml may be appropriate. In some cases such as injection (e.g. injection into a vein), an amount of 5 to 50 ml, or 10 to 45 ml, may be preferred. The volume may in some cases be in the range 100 to 1000ml, for example 250ml or 500ml, which may be applicable when provided for IV infusion for example. A typical injectable dose may be about 10ml or 15ml total, including an amount of iodide between any of the above minimum and maximum amounts (inclusive). In some embodiments, if the composition / formulation is to be used as an IV fluid infusion, then the active ingredient may be provided at a concentration of about 50mg per ml (which may be in 10 ml total). For example, 500mg of the active may be provided as a concentrate, which can be diluted into a volume of 250 ml sterile water. This may allow for an infusion rate of around 1-25mg per minute. In some embodiments, if the composition / formulation is to be used as an IV fluid injection, then a 10 ml single dose may contain around 465mg or 500mg of active ingredient. It will be appreciated that the exact dosage may vary according to clinical requirements, delivery route and the patient involved. The composition or formulation may in some embodiments contain alcohol. For example, there may be one or more simple alcohols, or one or more diols (particularly simple diols or glycol), or one or more triols (particularly simple aliphatic triols). Simple alcohols are considered to include ethanol, propanol and butanol (and / or the corresponding polyols). Other simple alcohols may be too toxic for potential safe use in humans and / or animals. If any polyols are present, then each alcohol I hydroxyl group in a given polyol may preferably be bonded to a different carbon atom or heteroatom than the other alcohol I hydroxyl group(s) of that molecule. If any alcohol(s) are present in the composition / formulation, then the alcohol(s) may optionally have been formed or generated in situ via one or more corresponding iodide precursors. If any polyols are present in the composition / formulation, then they should each be at concentrations which are below regulatory limits, and hence within safe I tolerable limits from a medical perspective. Ethylene glycol may be avoided. In other embodiments, the composition / formulation may be substantially free of alcohol (e.g. simple alcohols as noted above). Where diethanolamine is provided, the mass of diethanolamine may be approximately equal to, or less than, the mass of iodine or iodide present. There may be a margin of about 30% by mass or weight either way, for the mass of diethanolamine relative to the mass of iodine or iodide used. For example, in a composition / formulation for end use in an injection, the mass of diethanolamine (DEA) may be 30% less by weight than the weight of the iodide (which may be for the composition at pH 2-3). Note that additional DEA may be added to the composition / formulation prior to use, e.g. if the intended use involves subcutaneous or intramuscular injection. This may mean addition of DEA relative to a ‘storage’ version of the composition / formulation, which has no pH adjuster (or less than the amount of pH adjuster required for a particular use). Note that DEA and one or more other excipients may be added to the composition / formulation prior to use, e.g. if the intended use involves topical application. This may mean addition of DEA relative to a ‘storage’ version of the composition / formulation, which has no pH adjuster (or less than the amount of pH adjuster required for a particular use). The mass of ascorbic moiety or moieties present in the composition / formulation may be at least about half of the mass of iodide or iodine. Where ascorbic acid or ascorbate is used to reduce iodine, the mass of ascorbic acid or ascorbate should be sufficient to reduce substantially the entire amount of iodine to iodide, optionally with a small excess to ensure reduction of the entire amount. A suitable amount of water (most preferably pharmaceutical-grade water) may be provided in the pharmaceutical composition / formulation or the active ingredient portion of the composition / formulation. The term ‘pharmaceutical-grade water’ is intended to mean water than is sufficiently pure or free of contaminants to be suitable for medical use (particular medical use for humans), such as injection or topical application. Where ‘water’ is referenced in this specification, it is intended to refer to pharmaceutical grade water unless specifically noted otherwise. The mass of pharmaceutical grade water may be at least about any one of: 12, 20, 30, 40, 50, 60, 70 80, 90 or 100 times the mass of the iodide. This level of dilution may be used for an injection, for example. The mass of pharmaceutical grade water may be up to about 1000, 2000, 3000 or 4000 times the mass of iodide. This level of dilution may be used for an infusion, for example. In a particularly preferred embodiment, there may be a ratio (by weight) of 1 part ascorbic moiety to around 1.5 to 1.6 (preferably 1.555) parts iodine to around 18 to 20 (preferably 18.79) parts pure water. This provides sufficient ascorbic moiety and water to full convert the iodine to iodide. There is more water than strictly necessary for the reaction but it is provided for pharmaceutical reasons. Of course, it will be appreciated that the exact ratio may vary in other embodiments, according to the desired amount of iodine, and the amount of ascorbic moiety (or other pharmaceutically acceptable agent) needed to form iodide from that iodine in at least a minimum amount of water that avoids iodine precipitation. Selecting a correct ratio of iodine to ascorbic acid to water, for preparation of the composition / formulation, is important to ensure that the iodide (I-) is stable in solution. This avoids the risk of an ‘iodine clock’ style reaction. Indeed, the inventor has a sample - prepared from a given ratio of iodine to ascorbic acid to water - which still contains iodide and no iodine, even after over 10 months of exposure to heat and light. One embodiment of the composition I formulation (or part thereof) may be prepared by scaling the following amounts appropriately: - Iodine 1g (7.25%; moles = 1g / 126.9 = 7.88E-3) - Ascorbic acid 0.8g (including an assumed 12% moisture content) (5.79%; moles = 0.8g / 176.12 = 4.54E-3) - Water 12g (86.96%; moles = 12 / 18.02 = 0.67) The composition or formulation may have an osmolarity of substantially less than 1000 mOsmol / L. The osmolarity may optionally be at least about 200 mOsmol / L. The osmolarity may be about 500 mOsmol / L or less. In some preferred embodiments, the osmolarity of the composition or formulation may be about 300 to 400 mOsmol / L. One or more osmolarity modifiers (which may be stabilisers) may be used to adjust the osmolarity of the composition / formulation from an initial value. Any suitable modifier may be used. For example, if an initial value of active ingredient portion of 10 ml corresponds to 3.12757 mOsm / L at 13mg / ml, then the osmolarity may be increased using for example polyethylene glycol and / or propylene glycol. According to a third aspect of the present invention, there is provided a pharmaceutical composition or formulation for use as an active ingredient of a medicament or an active ingredient in therapy, the composition or formulation comprising: iodide (I-); an ascorbic moiety; and pharmaceutical-grade water. The advantages are similar to those described with respect to the first and second aspects above. The provision of the active ingredient composition / formulation as a standalone product is useful because it has been found to be stable enough for longterm storage prior to use. That is, the composition may be stable enough for weeks, months or years of storage, whilst maintaining its efficacy when subsequently used or made up for use as a medicament or in therapy. In particular, the ‘concentrated’ form of composition / formulation in this third aspect may be provided independently of the desired pH adjuster and / or excipient required for a particular use. When it is necessary to use the composition / formulation, it may be combined with inter alia the desired pH adjuster and / or excipient immediately or shortly prior to use. This is particularly preferred where the composition / formulation is intended for use by injection or infusion. For the avoidance of doubt, the third aspect of the invention may include any feature or features presented with respect to the first or second aspects of the invention. The same definitions given with respect to the first or second aspects of the invention apply to the third aspect. The iodide may be obtained by in situ reduction / reaction of iodine (or reduction or reaction of an iodide precursor) by a corresponding ascorbic moiety. The iodide may constitute up to about 10% by mass of the composition or formulation. The iodide may constitute up to about 9% or about 8% or about 7.5% or about 7% or about 6.5% or about 6% or about 5.5% or about 5% by mass of the composition or formulation. There may be at least about 0.025% or at least about 0.05% or at least about 0.1% iodide by mass in the composition or formulation. For example, in a 500 ml IV bag, 500mg of iodide may in solution be about 0.025% by mass. Where iodine is the source of iodide in the composition, the ascorbic moiety or moieties in the composition / formulation may constitute about the same percentage mass as the iodide, or may constitute a lower or higher percentage mass of the composition / formulation than the iodide. Preferably, if higher, then the excess is relatively small - perhaps up to around 10% or so higher. Having an excess of ascorbic moiety may be intended to ensure that all iodine or iodide precursor has been reduced to iodide or reacted to release iodide. If a different source of iodide or mixed sources of iodide are used, then a suitable amount of ascorbic moiety can be used to ensure that complete iodide generation, optionally with a small excess of ascorbic moiety as mentioned above. Some, most or substantially all of the iodide in the composition / formulation may be free iodide (which is discussed earlier in this specification). The composition or formulation may substantially lack free metal cations, for example there may be substantially few / no sodium and / or potassium ions. Preferably H+ is the main or only counter-ion present for iodide in the composition / formulation. The composition / formulation may include diethanolamine. The diethanolamine may be provided as a pH adjuster (to reduce the acidity of the active ingredient composition / formulation) and / or the diethanolamine may be provided as an excipient. Preferably the diethanolamine performs both functions. In some cases a different pH adjuster may be provided, and / or a different excipient may be provided. Where diethanolamine is provided, then it may constitute up to about 10% by mass of the composition or formulation. The diethanolamine may constitute up to about 9% or about 8% or about 7.5% or about 7% or about 6.5% or about 6% or about 5.5% or about 5% by mass of the composition or formulation. There may be at least about 0.0125%, or at least about 0.025%, or at least about 0.05% diethanolamine by mass in the composition or formulation. For example, in a 250ml IV bag, 326mg of DEA may be provided. If a different pH adjuster besides ethanolamine is desired, then a suitable amount of pH adjuster can be used to ensure that the desired pH (typically pH 1 to 6, preferably 2 to 5) is achieved for the particular application envisaged (such as injection, infusion, topical use, etc). Note that any suitable delivery route may be used, whether subcutaneous, intravenous, intradermal, intramuscular, via bolus or infusion, or otherwise. The pharmaceutical-grade water may constitute substantially most or all of the remaining percentage mass of the composition or formulation. The amount of water may depend on the form of the composition or formulation, e.g. whether it is for injection or infusion. The composition or formulation may consist only of the iodide, ascorbic moiety (or moieties), diethanolamine (or other pH adjuster), and the pharmaceutical-grade water, optionally with a pharmaceutically acceptable diluent and / or excipient and / or carrier. For example, the composition / formulation may include any one or more of the following as an inactive excipient: polyethylene glycol-300 USP (CAS: 25322-68-3); polyethylene glycol-400 USP (CAS: 25322-68-3); polyethylene glycol-600 USP (CAS: CAS: 25322-68-3), optionally to a maximum of 5% w / v; propylene glycol USP (CAS: 57-55-6), optionally to a maximum of 2% w / v; glycerin USP (CAS: 56-81-5). The iodide, the ascorbic moiety (or moieties) and a first portion of pharmaceuticalgrade water may be provided as a major aqueous portion of the composition or formulation. The major aqueous portion may be acidic, for example having a pH substantially in the range 1 to 3. The diethanolamine (or other pH adjuster) and a second portion of pharmaceuticalgrade water may be provided as a minor aqueous portion of the composition or formulation. The major aqueous portion may be at least 51% by mass of the composition / formulation, or may be between 55% to 95% by mass of the composition / formulation. The minor aqueous portion may be a corresponding percentage which together with the major aqueous portion sums to substantially 100% of the mass of the composition / formulation. Any one or more of a pharmaceutically acceptable diluent and / or a pharmaceutically acceptable excipient and / or a pharmaceutically acceptable carrier may be provided in or for the composition / formulation. Examples of possible carriers, diluents, solvents or vehicles include (but are not limited to): water, ethanol, one or more polyols (e.g. glycerin, propylene glycol, polyethylene glycol), vegetable-based oil, organic ester (e.g. ethyl oleate), and suitable combinations thereof. Any suitable adjuvant (e.g. preservative, wetting agent, emulsifying agent, dispersing agent) may be provided, if required. The composition or formulation may be suitable for use as an injectable or intravenous (IV) medicament, or subcutaneous medicament, or intramuscular medicament, or topical medicament. The composition or formulation may be in a form or container suitable for use as a topical medicament, such as any one or more of: cream, ointment, oil, foam, lotion, paste, powder, spray, aerosol, vapour, gel, solid, liquid, solution, suspension, emulsion, colloid, (transdermal) patch, dressing, bandage, fabric, sponge, tape, tincture, or in any other suitable form for application onto the skin. Where a dressing, bandage or fabric (or patch) is provided, it may be kept moist or damp or wet using water and / or another solvent. It may be kept from drying out prior to use. It may be kept from drying out both whilst in storage and during use (e.g. applied to a patient). This can mitigate formation of iodine from the iodide. In some cases, the dressing / bandage / fabric may be changed often enough that it does not substantially dry out, or the atmosphere may be humid enough to mitigate the issue. It is also possible to provide a covering for maintaining moisture in the dressing / bandage / fabric during use, and / or to use a dressing / bandage / fabric of a material which may lose moisture to the atmosphere at a slow enough rate to mitigate the issue. The composition or formulation may be provided in any suitable container(s). For examples concerning topical application in particular, the container may be any one or more of: a tube (such as a squeeze tube), a spray container (such as a pressurised spray container), a bottle (for example having a restricted aperture or atomiser), an applicator, or a tub. Preferably any of the containers has a seal, which may be a re-sealable seal. The composition or formulation may be suitable for use as an inhalable medicament. An inhaler or nebuliser may be provided which contains the composition / formulation. For example, an Omron (RTM) nebuliser may be used. A container or capsule of composition / formulation for fitting an inhaler or nebuliser may be provided. The composition or formulation may be provided for use in treating a condition, disease or infection caused by or resulting from a pathogen, such as a multi drug resistant pathogen or a multi antibiotic resistant bacterium. The pathogen may include a bacterium I bacteria, or a virus I viruses, or a fungus I fungi, or another micro-organism. The treatment may be for an acute or chronic condition, disease or infection. The composition or formulation may be provided for use in prophylactic treatment. The composition or formulation may be provided for use in treating a condition, disease or infection caused by or resulting from a pathogen selected from any or more of the group consisting of: Clostridium difficile’, Acinetobacter baumannii (beta-lactam resistant); Pseudomonas aeruginosa (optionally beta-lactam resistant); Cryptococcus gattif, Candida auris’, Aspergillus fumigatus’, Enterobacteriaceae (optionally ESBL-producing E. coliy, Enterococcus faecium (optionally vancomycin-resistant); Staphylococcus aureus (optionally methicillin-resistant); Neisseria gonorrhoeae (optionally tetracycline-resistant); Influenza’, Human Coronavirus; Mucor (optionally Mucor circinelloidesy Klebsiella pneumoniae’, Candida albicans (optionally multi-drug-resistant); Enterococcus hirae’, Enterococcus faecalis (or any vancomycin-resistant Enterococcus (VRE)); Escherichia coir, Mycobacterium terrae. Preferably, the pharmaceutical composition / formulation may be used or prescribed as a medicament against one or more qualifying pathogens as defined by the FDA Qualified Infectious Disease Product (QIDP) list (with reference to 21 CFR 317.2). The list is currently understood to include the following: Acinetobacter species, Aspergillus species, Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium difficile, Coccidioides species, Cryptococcus species, Enterobacteriaceae, Enterococcus species, Helicobacter pylori, Mycobacterium tuberculosis complex, Neisseria gonorrhoeae, Neisseria meningitidis, Non-tuberculous myco-bacteria species, Pseudomonas species, Staphylococcus species, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Vibrio cholerae. Note that instances of ‘species’ are intended refer generally to any species within the given genus, and particularly to species which are harmful to health. Preferably, initial indications for PN13 may be independently selected to include any one or more of the following group: Clostridium difficile, Acinetobacter baumannii (optionally beta-lactam resistant), Pseudomonas aeruginosa (optionally beta-lactam resistant), Cryptococcus gattii, Candida auris, Aspergillus fumigatus, Enterobacteriaceae (optionally ESBL-producing E.coli), Enterococcus faecium (optionally vancomycin-resistant), Staphylococcus aureus (optionally methicillin-resistant), and Neisseria gonorrhoeae (optionally tetracycline resistant). The pharmaceutical composition / formulation may be used or prescribed as a medicament against any one or more infectious pathogens listed under the FDA Orphan Drug Designation (ODD) criteria. According to a fourth aspect of the invention, there is provided a kit, container, inhaler, nebuliser or syringe of a pharmaceutical composition or formulation according to any of the preceding aspects of the invention. The advantages are similar to those discussed for the other aspects of the invention. The active ingredient(s) - or particularly the iodide - may be provided in a first chamber of the kit, container or syringe. The pH adjuster or pH-adjusting excipient may, where provided, be provided in a second chamber of the kit, container or syringe. Either or both these features can be useful to prolong the shelf-life of the active ingredient for reasons discussed earlier in this specification. The first and second chambers may be provided as part of a single container or syringe. If so, the first and second chambers may be adjacent to and / or in-line with each other for ease of combining the chamber contents. For example, a dual-chamber syringe (particularly dual liquid / liquid chamber) may be provided, such as the Companion® Dual Chamber Reconstitution Syringe currently available from the US company Credence MedSystems. Having a dual chamber syringe pre-filled with the composition / formulation has two particular advantages. It allows the active ingredient portion and pH adjustment portion of the composition / formulation to be provided in isolation from each other to maximise long-term stability of the active, and it can also make it much easier (compared to multi-vial preparation) for a nurse or other medical professional / practitioner to readily prepare or prime the pharmaceutical composition / formulation for use in an injection or infusion. The first and second chambers may each be provided in separate containers. Any or all of the containers may have a syringe-compatible seal for allowing withdrawal of the chamber contents by syringe. The active ingredient can be withdrawn from the first chamber / container by syringe. It can then be injected / transferred into the second chamber / container to form the pharmaceutical composition / formulation. This can be followed by withdrawal of the ready-to-use composition / formulation by syringe from the second chamber / container. The syringe of pharmaceutical composition or formulation can then be injected or infused as needed. According to a fifth aspect of the present invention, there is provided a method of manufacturing a pharmaceutical composition or formulation, comprising the steps of: a) forming or generating iodide (I-), preferably in situ, by mixing iodine (I2) or an iodide precursor with a pharmaceutically acceptable agent, which may include an ascorbic moiety such as any one or more of the group comprising an ascorbic acid, a dehydroascorbic acid or one or more other oxidation derivatives of ascorbic acid or a pharmaceutically acceptable salt of any of the group; and b) packaging the pharmaceutical composition or formulation. The advantages of this aspect are similar to those discussed for the preceding aspects. The mixing in step (a) may include mixing in an amount of pharmaceutical-grade water. Preferably, the amount used is at least a minimum amount to fully dissolve or solvate the amount of iodide (or any applicable precursor) and the amount pharmaceutical agent (or related derivative). In some embodiments, the amount of pharmaceutical grade water may be above the minimum required amount, in order to facilitate later dilution or mixing with another The packaging step may include packaging a pH adjuster or pH-adjusting excipient into a secondary package or compartment. That is, a secondary region which is isolated from or separate to the region containing the iodide. This is suitable for embodiments where longer-term storage of the composition / formulation is envisaged or desired. The iodide (and pharmaceutically acceptable reagent e.g. ascorbic moiety) is kept apart from the pH adjuster and so better retains its potential efficacy as discussed with respect to earlier aspects of the invention. The pharmaceutical composition or formulation may be the composition / formulation of any of the other aspects of the invention. According to a sixth aspect of the invention, there is provided a method of preparing a medicament, comprising the steps of: a) providing a pharmaceutical composition or formulation which comprises iodide (I-), and a pharmaceutically acceptable agent which may include an ascorbic moiety such as any one or more of the group comprising an ascorbic acid, a dehydroascorbic acid or one or more other oxidation derivatives of ascorbic acid or a pharmaceutically acceptable salt of any of the group; and b) adding a pH adjuster to the pharmaceutical composition or formulation to provide the medicament. The advantages of this aspect are similar to those discussed for the preceding aspects. In particular, this method can allow for a pharmaceutical composition / formulation with a relatively long shelf-life to be readily prepared into a medicament for immediate use. It will be appreciated that the pH adjuster may be added prior to expected administration of the medicament to a patient, or that a pH adjuster may be provided for mixing with the composition / formulation in a line for connection to a patient, for example. That is, an infusion bag may not necessarily have the pH-adjusted composition / formulation, but the pH adjuster could be provided in a second infusion bag whose line is subsequently linked up with the line from the composition / formulation infusion bag prior to the medicament reaching a patient-end of the relevant apparatus (such as a cannula). The mass or volume of pH adjuster added may be less than the mass or volume of the pharmaceutical composition or formulation. Adding the pH adjuster may increase the pH of the pharmaceutical composition or formulation. The pharmaceutical composition or formulation may be acidic. Having an acidic iodide portion of the composition / formulation is preferred for long-term stability of the iodide. The pH adjuster may be alkaline. The resulting medicament may be acidic (c. pH 1 to 6). Preferably the resulting medicament has a pH in the range 2 to 5, or 3 to 5, or 4 to 5. The pharmaceutical composition or formulation may be provided in a syringe or vial or container or transdermal patch prior to or during step (a). The medicament may be put into a syringe or vial or container or transdermal patch during or after step (b). The pharmaceutical composition or formulation may be the composition / formulation of any of the other aspects of the invention. According to a seventh aspect of the invention, there is provided use of an ascorbic acid or ascorbate or other ascorbic moiety to generate a therapeutic amount of iodide (I-) from iodine (I2) and / or an iodide precursor in a pharmaceutical composition or formulation for use as a medicament or in therapy. According to an eighth aspect of the invention, there is provided use of a pharmaceutically acceptable agent to generate iodide (I-) (preferably free iodide) from iodine (I2) and / or an iodide precursor in a pharmaceutical composition or formulation for use as a medicament or in therapy. The advantages of the seventh and eighth aspects of the invention are broadly the same as those discussed for the preceding aspects. According to a ninth aspect of the invention, there is provided a method of preparing or protecting any one or more of an organ, a tissue and / or bodily fluid (such as blood or plasma) for transport or transplant or transfusion or storage, the method comprising at least one of: a) injecting or infusing or applying a composition or formulation (of a preceding aspect) to the organ or tissue or bodily fluid ex vivo, b) using a composition or formulation of a preceding aspect to immerse or coat or wash or clean the organ or tissue or bodily fluid ex vivo, the composition / formulation optionally being provided as a solution I flush in a container or conduit. This has the advantage of killing microorganisms in I on the organ or tissue or bodily fluid, which may otherwise affect viability. This applies to transport of the organ / tissue / fluid, which can sometimes take hours, and / or to preparation of the organ / tissue immediately prior to transplanting or transfusing the same into a patient. The rapid action of the composition / formulation of the invention can therefore substantially improve the viability of such an organ / tissue both by prolonging the viability during transport and by mitigating transfer of pathogens into a transplant patient. The method may be considered as a method of processing blood or plasma for clearing the blood / plasma of potentially infectious or transmissible pathogens. This may be done when preparing blood prior to storage in suitable package / container. It may be done when preparing blood for transfusion (which may or may not be immediate). Preferably it is done prior to storing the blood / plasma to minimise delays in preparing fresh blood / plasma for a transfusion during an emergency such as a patient in a lifethreatening condition in need of an urgent transfusion. According to a tenth aspect of the invention, there is provided a container of blood or plasma or a tissue or an organ (ex vivo) which comprises the pharmaceutical composition / formulation of a preceding aspect. According to an unclaimed aspect of the present invention, there is a provided a method of transplanting an organ or tissue prepared or protected according to the ninth or tenth aspects, and carrying out the steps necessary to transplant the organ or tissue into a patient’s body. According to an unclaimed aspect of the present invention, there is a provided a method of transfusing blood or plasma prepared or protected according to the ninth or tenth aspects, and carrying out the steps necessary to transfuse the blood or plasma into a patient’s body. According to an unclaimed aspect of the present invention, there is a provided a method of administering a medicament comprising pharmaceutical composition or formulation to a patient, the method comprising the steps of: a) preparing a syringe or vial or container or transdermal patch or dressing or bandage or fabric containing the pharmaceutical composition / formulation of any preceding aspect; or otherwise providing the medicament; b) injecting or applying the medicament (directly or by means of any of the patch or dressing or bandage or fabric): i) into or onto the patient (e.g. into a blood vessel or vein, or below the skin (subcutaneously), or intramuscularly, or onto the skin, or possibly via a dialysis machine where the medicament may be introduced into the patient’s blood ex vivo)', or ii) into an infusion bag, which may be currently or subsequently set up as a drip to the patient (e.g. via a cannula or other intravenous (IV) line). For example, putting a wound dressing over a wound can help to prevent or treat an infection in the wound. The dressing or bandage or fabric may be impregnated with or soaked in the composition prior to application. The dressing / bandage / fabric may be kept moist or damp or wet, e.g. using water. This can avoid the iodide converting to iodine. The dressing / bandage / fabric may be changed for a replacement dressing or bandage or fabric which comprises the composition / formulation. According to an unclaimed aspect of the present invention, there is a provided a method of administering a medicament comprising pharmaceutical composition or formulation to a patient, the method comprising the steps of: a) connecting to a patient, for example by an IV drip line, an infusion bag containing the pharmaceutical composition / formulation of any preceding aspect; and / or b) replacing an infusion bag connected to a patient with a replacement infusion bag containing the pharmaceutical composition / formulation of any preceding aspect. According to an unclaimed aspect of the present invention, there is prescription of a medicament comprising pharmaceutical composition or formulation according to any preceding aspect to a patient. The medicament is preferably packaged and / or sealed, and may preferably be provided with instructions for use as a pamphlet and / or on a packaging surface, or accessible via an app (which may be accessible e.g. by QR code or a URL). For the avoidance of doubt, any aspect of the invention may without limitation include any feature or independently selected combination of features presented in relation to any other aspect or aspects of the invention. DESCRIPTION OF THE DRAWINGS For a better understanding of the present invention, and to show more clearly how it may be carried into effect, reference will now be made by way of example only to the accompanying drawings, in which: Figure 1 shows a flowchart of steps to manufacture a product or medicament comprising a pharmaceutical composition of formulation according to the present invention. DESCRIPTION OF PREFERRED EMBODIMENTS In this specification, various terms of art are used and, whilst known to the skilled person, definitions of the various terms are set out below for clarity. Definitions Throughout this specification, the term ‘iodide’ is intended to refer strictly to I; unless specifically stated otherwise. In particular, reference to iodide in this specification specifically excludes triiodide (l3‘). Throughout this specification, the term iodine is intended to refer strictly to I2 (also known as diiodide), unless specifically stated otherwise. The term ascorbic moiety is intended to mean anyone or more of the group comprising: an ascorbic acid, a dehydroascorbic acid or one or more oxidation derivatives (particularly a directive oxidation derivative) of ascorbic acid, or a pharmaceutically acceptable salt (e.g. an ascorbate) of any of the group. This includes various atom and / or group substitutions or additions which do not substantially change the chemistry of the ascorbic moiety. In particular, substitutions or additions which do not substantially prevent the ascorbic moiety from reducing iodine to iodide and which do not make the ascorbic moiety bio-incompatible or excessively toxic. Throughout the specification, any compound or combination compounds may be of pharmaceutical-grade quality or purity to ensure suitability for use in or on a human or animal. Manufacture of the pharmaceutical composition / formulation may be conducted in a pharmaceutical-grade environment (in terms of any of cleanliness, equipment standards, quality assurance checks and so on), such as a clean room, laboratory or any other suitable factory. Preparation or use of the invention may be conducted in a medical environment. The term “pharmaceutically acceptable salt” is used in relation to ascorbic moiety to mean a salt (e.g. ascorbate) which is capable of reducing iodine to iodide or of releasing iodide from another iodide precursor, whilst being at a biologically tolerable level and in a biologically tolerable form fora patient. Information on pharmaceutically acceptable salts may be found in Remington’s Pharmaceutical Sciences (19th Edition, Mack Publishing Co., Easton, PA 1995). Regarding solid forms of compositions / formulations according to the invention, any crystalline or polymorphic form is intended to be within the scope of the claims. The term “therapeutically effective” is intended to mean that, for whatever amount is at issue, it leads to a sufficiently high reduction in the amount target pathogen to facilitate treatment of and ideally recovery from whatever infection, condition or disease is being caused by that pathogen. The effective amount may be provided in one dose or a plurality of doses. The effective amount may at least relieve symptoms for a patient, or at least stabilise or slow / delay progression of the infection / condition / disease, but is intended to preferably reverse or cure the infection / condition / disease. Compositions / formulations according to the invention can be prepared and administered in any manner which makes the active ingredient(s) bioavailable. A person skilled in the art of preparing compositions / formulations may determine a suitable administration based on the pathogen (or symptoms / conditions observed) to be treated and the patient involved. Further information may be obtained from Remington’s Pharmaceutical Sciences (19th edition, Mack Publishing Co. (1995)). The compositions / formulations can be prepared using techniques well known in the art, optionally using any suitable a pharmaceutically acceptable carrier, diluent or excipient. Preparation of compositions / formulations of the invention The present invention is based on the provision of iodide (I-) in a composition or formulation at a therapeutically effective level, preferably in combination with ascorbic acid or another suitable ascorbic moiety, and preferably where the iodide is derived in situ reduction of iodine. The principle chemical reaction relating to such preferred embodiments is depicted by the equation below: In carrying out the reaction, iodine (CAS: 7553-56-2) is reacted with ascorbic acid (CAS:50-81-7). This can be done using any suitable apparatus or equipment, including a reaction vessel and any one or more of a stirring means, heating means, and / or inert gas supply. The reaction is done in a certain amount of water to allow the reaction to occur, which may be a minimum amount of water. This oxidises the ascorbic acid to dehydroascorbic acid (CAS: 490-83-5) in aqueous solution. Simultaneously, two electrons (e-) from the two hydrogens released during oxidation are donated to the 12 in aqueous solution, thus reducing iodine to form two iodide ions (CAS: 20461-54-5). The ascorbic acid used in the above reaction should ideally be highly concentrated (optionally solid ascorbic acid can be used). This helps to reduce the iodine to a nano particulate form in solution. It is still ‘visibly’ an iodine solution, that is a yellow solution. Note that until sufficient water has been added, it would form a black solution on mixing with starch due to incomplete reduction (although no starch is actually used during preparation of the composition / formulation). That is, non-reacted iodine would, if added, associate with iodide and form a triiodide complex with starch. It will be appreciated that in determining preferred reaction conditions such as mixing speed and reaction time that an indicator such as starch may be used during process optimisation. Once sufficient water has been added to allow the reaction to occur and complete -i.e. to reduce all of the iodine (I2) to iodide (I-) - then the solution turns clear. At this stage, with no iodine remaining, the solution would no longer turn black if starch s added. It will be appreciated that another solvent which permits the reaction to occur to completion and is bio-compatible or bio-tolerated, or can be readily removed and replaced with a bio-compatible / tolerated solvent which does not destroy the iodide, can be used. The reactants and water used should be of pharmaceutical grade purity when preparing the composition / formulation for use in / on a patient. Rather than necessarily adding a pH adjuster to the iodide / ascorbic acid composition straightaway, it has been found preferable in some embodiments to manufacture the composition / formulation in two portions. This maintains pH stability of the active ingredient during storage (particularly long term storage). The two portions can be stored separately (or in isolation from each other). For example, they can be provided as two separate vials or in a dual-chamber syringe for mixing directly before use. It is thus possible to provide (i) a highly stable active portion which includes iodide (I-), dehydroascorbic acid (optionally with some residual ascorbic acid) and water at a pH of 1, and (ii) a pH adjuster portion at alkaline pH (e.g. pH 11). When mixed at or just prior to the point of use, a pharmaceutical composition / formulation (or medicament) is obtained which has a pH of around 1 to 6, or in preferred embodiments 2 to 5, or in some particularly preferred embodiments 2-3 or4.5±0.5. Various tests during development of the invention yielded pH values in the range pH 4 to 7. The exact pH depended on whether it is tested immediately after mixing (which is most feasible if using a dual chamber syringe) or up to 30 minutes after mixing (e.g. if using multi vial mixing). Alternatively, the composition / formulation (or medicament) can be prepared and packaged / sealed in a container. This may be preferred when provided for topical application, for example, where the shelf-life may be shorter but it is ready-to-use by a patient. Figure 1 depicts a flowchart which indicates each of these preparatory routes at a high level. Example 1 A first example composition / formulation (1) was made from two parts - an 8g active ingredient portion A and a 2g pH-adjusting portion B. This 10g example was formulated to be suitable for injection. Portion A was prepared by dissolving or dispersing 0.100g of I2 and 0.073g CeHsOe (ascorbic acid) in 7.827g H2O. Portion B was prepared by dissolving or dispersing 0.070g diethanolamine (DEA) in 1.93g H2O. Once portions A and B were mixed together, the resulting composition / formulation had an osmolarity of about 307 mOsmol / L. The solution was either colourless or faintly yellow. Note that the above example composition / formulation has all inactive ingredients in amounts which are below the FDA acceptable limits for IV injectables, as well as meeting stability and safety requirements. Even so, the efficacy of this exemplary PN13 formulation is not significantly impacted when compared to placebo versions. Example 2 A second example composition / formulation (2) was made from 0.465g iodide (prepared from a corresponding amount of iodine and ascorbic acid) plus 0.326g of DEA, in a suitable amount of water. This gives one preferred molar ratio of iodide to DEA. The second example was prepared in an analogous manner to the first example. It will be appreciated that a corresponding amount of iodide may be prepared from another suitable precursor using ascorbic acid or another ascorbic moiety / pharmaceutically acceptable agent, although the amounts of reagent used and the amount of water required would need to be adjusted. It will be appreciated that other example formulations can be made within the scope of the disclosure herein, and that concentrate or diluted forms of the composition / formulation can be provided as needed. Proposed dosage and delivery route Use for treating active infection by a pathogen In some embodiments, a preferred delivery route for the composition / formulation is intravenous injection. The test compositions / formulations (variously referred to as PN13, followed by a reference number of “.XXX” where XXX represents three numerals) have been developed for IV injection or infusion or another delivery route, although the final injectable / other dosage form and its dosing amount and regime will be finalised following human trials. For IV infusion, one potential option is treatment by a dose of 1.86mg / mL (of the active ingredient) as a 250ml intravenous (IV) infusion. This corresponds to a dose of iodide of 465mg total (per infusion). For IV injection, one potential option is treatment by a dose of 130mg (of the active ingredient) as a 10ml intravenous (IV) injection. This corresponds to a dose of iodide of 13mg / ml. In each case, this can be achieved by slightly modifying composition / formulation in Example (1) to increase the amounts of iodine and ascorbic acid used, and slightly reducing the amount of water (specifically in the amounts given for Example (1)). The amount of DEA can be adjusted as needed according to the desired pH of the medicament to be injected. For IV injection, a second potential option is treatment by a dose of 465mg (of the active ingredient) as a 15ml intravenous (IV) injection. This corresponds to a dose of iodide of 31mg / ml. It will be appreciated that the amount of iodide used may be higher or lower than these particular examples, as long as the dose is sufficient to achieve the desired therapeutic effect and is not so high as to be fatal to the patient or cause significant secondary complications / harm to the patient. In this regard, it is expected that the amount of iodide in a given dose will be above about 1mg. It may be that amount of iodide in a given dose will be below about 5000mg. Use for prophylactic treatment or supporting treatment It is envisaged that compositions / formulations according to the invention are suitable for prophylactic use. Such use may be particularly preferred for vulnerable patients (e.g. babies, children and / or the elderly (such as those aged 65 and over)) and / or frail patients (such as those with underlying and / or chronic medical conditions), and / or immunosuppressed patients (such as those undergoing chemotherapy and / or radiotherapy). PN13 has been shown to be non-toxic and so it may feasibly be used to support another treatment regimen; for example, during cancer treatment or immunotherapy. This could be undertaken in order to mitigate detrimental impact to the concurrent treatment(s), which might otherwise occur e.g. if a low level underlying infection or ‘hospital bug’ took hold in the patient whilst they were immunocompromised. For example, an initial treatment regimen of 1.86mg / mL (of active ingredient) in 250ml intravenous (IV) infusion may be used to clear a low level or underlying infection. The treatment may be repeated after 7 days, or every 7 days, for whatever duration is preferred or necessary. This may be for a similar duration or longer to the period for which the patient is undergoing chemotherapy and / or radiotherapy, for example. Biocompatibility data The Applicant believes that only limited clinical trials will be required to establish suitable biocompatibility and safety of the present invention. This is because there is already a substantial amount of data available for the safety, pharmacokinetics and pharmacodynamics (PK / PD) of the active pharmaceutical ingredient(s) (API(s)) of PN13. An infusion of composition / formulation according to Example (1) above can be provided at a dosage of 1.86mg active per mL for an intravenous (IV) infusion. At a multiple of 17.5 times the intended active concentration dose, such an infusion of PN13 is rated as moderate (tested to ISO 10993-5 in vitro cytotoxicity). An injectable composition / formulation according to Example (1) above can be provided at a dosage of 10.3mg active per mL for intravenous (IV) injection. At a multiple of 3.1 times the intended active concentration dose, such an injection of PN13 is rated as moderate (tested to ISO 10993-5 in vitro cytotoxicity). Test compositions / formulations The following test articles were prepared and tested against the various pathogen samples set out in the following description. Test articles of the “active” type below are compositions / formulations according to the invention and include iodide (I-). Test 5 articles of the “control” type below are not compositions / formulations according to the invention. Composition / formulation Type Constituents PN13.001 Active - Iodide Made from Iodine, pure water, ascorbic acid PN13.002 Active - Iodide Made from Iodine, pure water, ascorbic acid PN13.003 Active - Iodide Made from Iodine, pure water, ascorbic acid PN13.004 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing PG (propylene glycol) PN13.005 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing PG (propylene glycol), PEG-300 (polyethylene glycol 300) PN13.006 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing PG (propylene glycol), PEG-300 (polyethylene glycol 300), glycerin and Laponite EP PN13.007 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing (propylene glycol), PEG-300 (polyethylene glycol 300) and glycerin PN13.008 Control Ascorbic acid only, with a pH range of <4 PN13.009 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing PG (propylene glycol), PEG-300 (polyethylene glycol 300) PN13.010 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing PG (propylene glycol), PEG-300 (polyethylene glycol 300) PN13.011 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing PG (propylene glycol), PEG-300 (polyethylene glycol 300) PN13.012 Active - Iodide Made from Iodine, pure water, ascorbic acid and containing (propylene glycol), PEG-300 (polyethylene glycol 300) and glycerin PN13.013 Control Ascorbic acid only, with a pH range of <4 PN13.014 Control Dehydroascorbic acid only PN13.015 Active - Iodide Made from Iodine, water, ascorbic acid, with a pH of 2.5 PN13.016 Control Made from Ascorbic acid and sodium bicarbonate as a pH buffer, having a pH of 5.3 PN13.017 Control Potassium iodide PN13.018 Active - Iodide Made from Iodine, water, ascorbic acid, with a pH of between 5-6 with sodium bicarbonate PN13.019 Active - Iodide Made from Iodine, water, ascorbic acid and DEA, pH 2 PN13.020 Active - Iodide Made from Iodine, water, ascorbic acid and DEA, pH 2.5 PN13.021 Active - Iodide Made from Iodine, water, ascorbic acid, pH 1.9 Testing protocols RG220013A Protocol Summary The RG220013A testing protocol is a suspension time-kill test of fungicidal or bactericidal activity. The purpose was to evaluate the antimicrobial efficacy of one test article against clinically relevant microorganisms, when conducted in accordance with Good Laboratory Practice Standards (GLPs) stipulated by 21 CFR Part 58 with American Culture Collection (ATCC) microorganism strains. The percent reduction and log™ reduction, when compared to an initial numbers control, were determined for each challenge species following the product exposure times. The relevant protocol steps were: • A microbial culture was prepared. • Each test product (i.e. the composition I formulation) was evaluated at three concentrations, with the following parts in the three test solutions: o 8 parts of the test product was added to 1 part test microorganism and 1 part interfering substance (in this case, human blood plasma). o 6 parts of the test product is added to 1 part test microorganism and 1 part interfering substance (in this case, human blood plasma) and 2 parts sterile water. o 4 parts of the test product is added to 1 part test microorganism and 1 part interfering substance (in this case, human blood plasma) and 4 parts sterile water. This was done in sufficient sterile test vessels - enough to account for all replicates that were to be performed and then immediately mixed. • After the predetermined contact time(s), at a determined temperature(s), small aliquots of the mixture of fungus / yeast / bacteria and product were removed, chemically neutralized, and microorganisms were enumerated. • Neutralization controls were run as appropriate. • At the highest concentration tested, the test product needed to demonstrate >10% reduction compared to controls. • Results were presented in Log reduction and percentage reduction form. The general neutraliser in the test embodiments included: Lecithin 3g / l, polysorbate 80 30g / l, sodium thiosulphate 5g / l, L-histidine 1g / l, saponin 30g / l, and phosphate buffer powder 0.35g / l. Preparation of Test Inocula • Individual liquid stock cultures of each test microorganism were prepared from the most recent monthly working stock culture or a frozen library stock culture to a sufficient volume of an appropriate growth broth / medium. They were incubated under conditions appropriate to allow for the growth of the target microorganism, (i.e., temperature, anaerobic / aerobic conditions, etc.). • Test culture tubes were vortex mixed and diluted (if appropriate) in a sufficient volume of sterile Phosphate Buffered Saline (PBS) such that an inoculum concentration of 1.5 x 107 CFU / ml to 5.0 x 107 CFU / ml was targeted. • The final test inoculum was vortex-mixed prior to use and test inoculum suspensions were used within 2 hours of preparation. The final test inoculum is referred to as test culture suspension N. Preparation of Test Articles • The test article was prepared in sterile water at a minimum of three different concentrations to be evaluated separately. The test article was to be evaluated at its concentration as-received (e.g., undiluted before mixing in test solution), and in this case the highest tested concentration was 80% of the RTU (where RTU means ready-to-use, which is the undiluted test article). Calculations If enumerations were performed manually using serial dilutions, then: [(Plate Count 1 + Plate Count 2) / 2] x dilution factor of plating = CFU / ml where CFU means Colony Forming Unit. If enumerations were performed using an automated spiral plater, the CFU / ml was calculated per plate, for example via a SphereFlash® automated colony counter, and averaged for duplicate plates. Dilution in neutralizer or as a result of other testing steps was accounted for in calculating CFU / ml by multiplying the result of the above calculation, or the output of the SphereFlash® automated colony counter, by the factor of dilution. For example, enumeration of the inoculum used in Test Na yields No, the CFU / ml of the test mixture at the beginning of the contact time (time zero) was calculated by: No = [[(Plate Count 1 + Plate Count 2) / 2] x dilution factor of plating] * 10'1 where No represents the CFU / ml of the test mixture at the beginning of the contact time, or time zero. It is equivalent to N * 10'1 as a result of dilution by the addition of the test article and interfering substance. / Wo was calculated for evaluation of controls A, B, and C by applying the dilution factor used in each control to the calculated Nvor Nvb. Log Reductions were calculated as follows: LR = mean log™ (No) - mean log™ (Na) where LR = Log™ Reduction relative to the CFU / ml of the test mixture at the beginning of the contact time. Percent Reductions were calculated as follows: Percent Reduction (%) = 100 x (1 - 10'LR) Success Criteria The experimental success (controls) criteria were as follows: • The following inoculum titres were targeted in conduct of testing and study controls: o N is between 1.5 x 107 and 5.0 x 107 and No is between 1.5 x 106 and 5.0 x 106. o Nv is between 3.0 x 102 and 1.6 x 103. o Nvb is between 3.0 x 104 and 1.6 x 105. • Controls A, B, and C are confirmed to meet the following: o A, B, and C are greater than or equal to O.5*Nvo. • Sterility controls for media and reagents must be negative for growth of the test microorganisms. • The positive (growth) controls must be positive for growth and must demonstrate a pure culture of each test microorganism. • Methicillin-resistance is confirmed for Staphylococcus aureus ATCC 33591 where the zone of inhibition surrounding a 30pg cefoxitin disk is <21 mm in diameter after 16-18 hours incubation. The product performance success criteria were as follows: • At the highest concentration tested, the product needed to demonstrate >10% reduction compared to No. Elements of the above protocol summary (preparation of test inocula, preparation of test articles, calculation methods, success criteria) were also used in the following other test protocol summaries to the extent needed. RG220013B Protocol Summary The RG220013B testing protocol is a suspension time-kill test of fungicidal or bactericidal activity from topically applied products. The purpose was to evaluate the antimicrobial efficacy of one test article against clinically relevant microorganisms, when conducted in accordance with Good Laboratory Practice Standards (GLPs) stipulated by 21 CFR Part 58 with American Culture Collection (ATCC) microorganism strains. The percent reduction and log™ reduction, when compared to an initial numbers control, were determined for each challenge species following the product exposure times. The relevant protocol steps were: • A microbial culture was prepared, and equal volumes of the test product were placed in sufficient sterile test vessels - enough to account for all replicates that were to be performed. • A volume of microbial culture (usually one tenth (1 / 10) or less of the product volume) was placed in the test vessel and then immediately mixed. • After the predetermined contact time(s), at a determined temperature, small aliquots of the mixture of bacteria / fungus and product were removed, chemically neutralized, and microorganisms were enumerated. • To measure initial microbial concentrations, a saline control was spiked with the same microbial culture and then enumerated. • Numbers of microorganisms in the reaction vessel were plotted over time. • Neutralization controls were run as appropriate. • At the highest concentration tested, the product needed to demonstrate >10% reduction compared to controls. • Results were presented in Log reduction and percentage reduction form. RG220013C Protocol Summary The RG220013C testing protocol is a quantitative suspension test of fungicidal or yeasticidal activity. The relevant protocol steps were: • A microbial culture was prepared. • 8 parts of the test product were added to 1 part test microorganism and 1 part interfering substance in sufficient sterile test vessels - enough to account for all replicates that were to be performed and then immediately mixed. • After the predetermined contact time(s), at a determined temperature(s), small aliquots of the mixture of fungus / yeast and product were removed, chemically neutralized, and microorganisms were enumerated. • To measure initial microbial concentrations, a saline control was spiked with the same microbial culture and then enumerated. • Numbers of microorganisms in the reaction vessel were plotted over time. • Neutralization controls were run as appropriate. • At the highest concentration tested, the product needed to demonstrate >10% reduction compared to controls. • Results were presented in Log reduction and percentage reduction form. RG220013D Protocol Summary The RG220013D testing protocol is a quantitative suspension test of bactericidal activity. The relevant protocol steps were: • A microbial culture was prepared. • 8 parts of the test product were added to 1 part test microorganism and 1 part interfering substance in sufficient sterile test vessels - enough to account for all replicates that were to be performed and then immediately mixed. • After the predetermined contact time(s), at a determined temperature(s), small aliquots of the mixture of bacteria and product were removed, chemically neutralized, and microorganisms were enumerated. • To measure initial microbial concentrations, a saline control was spiked with the same microbial culture and then enumerated. • Numbers of microorganisms in the reaction vessel were plotted over time. • Neutralization controls were run as appropriate. • At the highest concentration tested, the product needed to demonstrate >10% reduction compared to controls. • Results were presented in Log reduction and percentage reduction form. RG220013E Protocol Summary The RG220013E testing protocol is a quantitative suspension test of mycobactericidal activity. The relevant protocol steps were: • A microbial culture was prepared. • 8 parts of the test product were added to 1 part test microorganism and 1 part interfering substance in sufficient sterile test vessels - enough to account for all replicates that were to be performed and then immediately mixed. • After the predetermined contact time(s), at a determined temperature(s), small aliquots of the mixture of mycobacteria and product were removed, chemically neutralized, and microorganisms were enumerated. • To measure initial microbial concentrations, a saline control was spiked with the same microbial culture and then enumerated. • Numbers of microorganisms in the reaction vessel were plotted over time. • Neutralization controls are run as appropriate. • At the highest concentration tested, the product needed to demonstrate >10% reduction compared to controls. • Results were presented in log reduction and percentage reduction form. RG220013F Protocol Summary The RG220013F testing protocol is a quantitative suspension test of virucidal activity. The relevant protocol steps were: • A viral culture was prepared. • Test virus and interfering substance was added to pre-determined test product dilutions in sufficient sterile test vessels - enough to account for all replicates and controls required, and then immediately mixed. • After the predetermined contact time(s), at a determined temperature(s), small aliquots of the mixture of virus and product were removed, neutralized, and were enumerated by sterile serial titration onto cell monolayers. • The surviving virus tissue culture infective dose (TCID50) was determined by the appearance of cytopathic effect (CPE) on the cells and was calculated using the Spearman-Karber calculation. • Neutralization controls were run as appropriate. • At the highest concentration tested, the product needed to demonstrate >10% reduction compared to controls. • Results were presented in log reduction and percentage reduction form. Cytotoxicity Protocol Summary This protocol was used to evaluate any cytotoxic effect of the test product on the BALB / 3T3 cells (ATCC CCL163™) cell line according to ISO-10993-5:2009: cytotoxicity - direct contact test. The contact time was defined as 24 hours. The relevant protocol steps were: • From a BALB / 3T3 fibroblast culture, a suspension of 1 x 105 cells / mL were prepared and dispensed into two 12 well-plates subdivided into the following groups: GROUPS PLATE N.I GROUPS PLATE N.2 REPLICATES Blank Vehicle Negative Control Test Sample REPLICATES Blank Vehicle Positive Control Test Sample Blank Vehicle Negative Control Test Sample Blank Vehicle Positive Control Test Sample Blank Vehicle htegahve Control Test Sample i Blank Vehicle Positive Control Test Sample • 1.2mL of the cell suspension (1.2 x 105 cells / well) were pipetted into the Vehicle, Negative / Positive controls and Test Sample wells. • 1,2mL of supplemented culture medium alone (without cells) was pipetted into Blank wells. • The two plates were incubated at (37±1)°C in a (5±1)% CO2 atmosphere, allowing cell sedimentation and the constitution of a sub-confluent monolayer. • After 24 hours from cell seeding, the plates were observed to confirm 80% confluence and supplemented with culture medium (replaced with fresh 1.2 mL / well in all wells). • To Vehicle wells, an inert filter paper was placed in the middle of each well (6 replicates). • To Test Sample wells, 50pl of test sample was deposited onto the inert filter paper and then placed into the middle of each well (6 replicates). • Negative controls represented 50pl of DPBS (Dulbecco's phosphate-buffered saline) deposited onto the inert filter paper and then placed into the middle of each well (3 replicates). • Positive controls represented 50pl of 0.2-0.5% solution of SDS (sodium dodecyl sulphate) ISLS (sodium lauryl sulphate) deposited onto the inert filter paper and then placed into the middle of each well (3 replicates). • Plates were then incubated a thermostat at (37+1 )°C in a (5±1)% CO2 atmosphere for 24 hours. • After this contact time, the plate was observed under an inverted microscope and biological reactions were to be evaluated following a 0 to 4 scale according to ISO 10993-5:2009. • Each well was emptied, washed with DPBS and treated with 1200 pL of Neutral Red Medium for 3 hours at (37±1)°C in a (5±1)% CO2 atmosphere. Thereafter each well was washed with DPBS, totally dried and then treated with 1800 pL of NR Desorb Solution. The plates were put on an orbital shaker for at least 15 minutes to homogenize the solution. • The absorbance of the resulting solution was measured at 540 nm in a microtiter plate reader. • The achievement of a numerical grade greater than 2 was to be considered as indicating cytotoxic effect. • A cellular viability reduction >30% was to be considered as indicating a cytotoxic effect. Grade Reactivity Description of Reactivity Zone 0 None No detectable zone around or under specimen 1 Slight Some malformed ordegenerated cells under specimen 2 Mild Zone limited to area under specimen 3 Moderate Zone extending specimen size upto 1.0cm 4 Severe Zone extending further than 1.0cm beyond specimen Cytotoxicity results The results of the cytotoxicity tests are presented in Table 1 below: Test Article (PN13-Internal reference) Cell Line Used for assessment Contact Time Reactivity Grade (0-4) Active (mg / mL) Reactivity Description of Reactivity Zone PN13.011 BALB / 3T3 cells (ATCC CCL163™) 24 hours 3 32.5 Moderate Zone extending specimen size up to 1.0 cm PN13.012 BALB / 3T3 cells (ATCC CCL163™) 24 hours 0 3.25 None No detectable zone around or under specimen Table 1 - Cytotoxicity results for PN13.011 and PN 13.012 Efficacy results Overview Tables 2, 3 and 4 below provide an overview of the results of the tests carried out using PN13 on fungi, bacteria and viruses respectively; that is, using a 5 composition / formulation according to the present invention. Formulations were adjusted during the development process to take into account results of prior testing and analysis, allowing for the adjustment or removal of a number of excipients which have shown to have a negative effect on cytotoxicity and / or product 10 shelflife. The different formulations may be inferred from the change to the ‘internal reference’ portion of the Test Article number in the tables below. 15 As will be appreciated from each of Tables 2 to 4, there is surprisingly high or exceptionally high efficacy from the various PN13 compositions / formulations against every one of the fungi, bacteria and viruses tested, even for short contact times on a timescale of minutes or even seconds. Test Microorganisms (fungi) Testing Protocol Reference Test Article PN13-lnternal reference Contact Time Percentage Reduction Compared to Control Candida albicans ATCC 10231 RG220013C PN13.001 60 minutes 97.71% RG220013C PN13.005 10 minutes 99.89% Aspergillus brasiliensis ATCC 16404 RG220013C PN13.005 10 minutes 99.41% Mucor circinelloides NCPF 2708 RG220013C PN13.001 30 minutes 94.48% RG220013C PN13.005 10 minutes 99.56% Mucor circinelloides ATCC 24905 RG220013B PN13.006 180 minutes >99.998% RG220013A PN13.007 30 minutes >99.9995% 20 Table 2 - Overview of PN13 test results against selected fungi Test Microorganisms (bacteria) Testing Protocol Reference Test Article PN13-lnternal reference Contact Time Percentage Reduction Compared to Control Candida albicans ATCC 10231 RG220013C PN13.001 60 minutes 97.71% RG220013C PN13.005 10 minutes 99.89% Aspergillus brasiliensis ATCC 16404 RG220013C PN13.005 10 minutes 99.41% Mucor circinelloides NCPF 2708 RG220013C PN13.001 30 minutes 94.48% RG220013C PN13.005 10 minutes 99.56% Mucor circinelloides ATCC 24905 RG220013B PN13.006 180 minutes >99.998% RG220013A PN13.007 30 minutes >99.9995% Pseudomonas aeruginosa ATCC 15442 RG220013D PN13.002 10 seconds >99.9999% Enterococcus hirae ATCC 10541 RG220013D PN13.002 60 seconds >99.9999% Enterococcus faecalis (VRE) NC12201 RG220013D PN13.002 60 seconds 99.9999% RG220013D PN13.005 10 minutes >99.999% Methicillin-resistant Staphylococcus aureus (MRSA) NC 14402 RG220013D PN13.002 60 seconds 99.65% RG220013D PN13.005 10 minutes >99.999% Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 33591 RG220013B PN13.006 30 minutes >99.9994% RG220013A PN13.007 30 minutes >99.9997% Methicillin-resistant Staphylococcus aureus (MRSA) NCTC 12493 RG220013D PN13.008 180 minutes 99.99996% RG220013D PN13.013 180 minutes 99.997% RG220013D PN13.014 180 minutes 99.98% RG220013D PN13.015 180 minutes >99.99992% RG220013D PN13.018 180 minutes >99.997% RG220013D PN13.019 3 minutes >99.999% RG220013D PN13.019 30 minutes >99.999% RG220013D PN13.020 30 minutes >99.999% RG220013D PN13.021 3 minutes >99.976% RG220013D PN13.021 30 minutes >99.999% Escherichia coli K12 NC 10538 RG220013D PN13.002 60 seconds >99.9999% RG220013D PN13.005 10 minutes >99.999% Mycobacterium terrae ATCC 15755 RG220013E PN13.003 120 minutes 80.05% RG220013E PN13.004 120 minutes >99.9999% Table 3 - Overview of PN13 test results against selected bacteria Test Microorganisms (viruses) Testing Protocol Reference Test Article PN13-lnternal reference Contact Time Percentage Reduction Compared to Control Influenza A H1N1 A / PR / 8 / 34 RG220013F PN13.005 10 minutes >99.999% Human Coronavirus 229E RG220013F PN13.005 10 minutes >99.99% Table 4 - Overview of PN13 test results against selected viruses The exceptional results set out summarised above support use of the invention for any indication. It can be seen that inclusion of a certain excipient or excipients may enhance efficacy in some cases but that the underlying composition / formulation is still 5 highly effective at reducing the amount of micro-organism to an almost undetectable level in many cases. Compositions / formulations according to the invention and other related aspects of the invention are therefore contemplated as being important for treatments and / or 10 therapies to address health threats posed by micro-organisms, whether for use in their own right during a treatment / therapy or as a supporting or secondary treatment / therapy before, during and / or after another treatment / therapy. Testing Protocols and Standards Test Microorganism(s) or Purpose Protocol Name Contact Temperature Bacteria and Fungi RG220013A 37°C ±1°C Bacteria and Fungi RG220013B 37°C ±1°C Fungi RG220013C 20°C ±1°C Bacteria RG220013D 37°C ±1°C Mycobacteria RG220013E 20°C ±1°C Virus RG220013F 20°C ±1°C Cytotoxicity Testing ISO 10993-5:2009 37°C ±1°C Table 5 - Summary of test protocols and conditions used Raw efficacy data Tables 6 to 18 below provide the specific results of the tests carried out using PN13 on each of the selected fungi, bacteria and viruses respectively; where PN13 (followed 5 by a given reference number) is a composition / formulation according to the present invention. Tests for efficacy based on a topical route of delivery are set out in Table 19 below. In these tests, PN13 included a further excipient which acted as a rheology modifier, and 10 showed excellent efficacy in testing. The modifier in these tests was from Laponite (RTM), specifically the Laponite-EP rheology modifier based gel. That is, an organically-modified synthetic phyllosilicate. Test Microorganism FUNGUS Test Article PN13 Contact Time Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero - Test Culture Suspension N Enumeration 9.39E+07 8.39 - - Candida albicans ATCC 10231 PN13.001 30 minutes 8.90E+07 7.95 63.67% 0.44 60 minutes 5.60E+06 6.75 97.71% 1.64 - Test Culture Suspension N Enumeration 9.72E+07 8.72 - - Mucor circinelloides NCPF 2708 PN13.001 10 minutes 3.25E+07 7.51 93.81% 1.21 30 minutes 2.90E+07 7.46 94.48% 1.26 60 minutes 2.80E+07 7.45 94.60% 1.27 Table 6 - PN13.001 test results against Candida albicans and Mucor circinelloides Test Microorganism BACTERIA Test Article PN13 Contact Time Test Concentrations (%) Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 9.38E+07 8.38 Pseudomonas aeruginosa ATCC 15442 PN13.002 10 seconds 80% 1.4E+02 <2.15 >99.9999% >6.23 75% 1.4E+02 <2.15 >99.9999% >6.23 50% 1.4E+02 <2.15 >99.9999% >6.23 60 seconds 80% 1.4E+02 <2.15 >99.9999% >6.23 75% 1.4E+02 <2.15 >99.9999% >6.23 50% 1.4E+02 <2.15 >99.9999% >6.23 600 seconds 80% 1.4E+02 <2.15 >99.9999% >6.23 75% 1.4E+02 <2.15 >99.9999% >6.23 50% 1.4E+02 <2.15 >99.9999% >6.23 Table 7- PN13.002 test results against Pseudomonas aeruginosa Test Microorganism Test Article Contact Time Test Concentrations (%) Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 9.47E+07 8.47 Enterococcus hirae ATCC 10541 PN13.002 10 seconds 80% 1.20E+08 8.08 59.32% 0.39 75% 3.75E+08 8.57 No Reduction -0.10 50% 3.30E+08 8.52 No Reduction -0.05 60 seconds 80% 1.40E+02 <2.15 >99.9999% >6.32 75% 2.41E+07 7.38 91.83% 1.09 50% 7.50E+07 7.88 74.58% 0.59 600 seconds 80% 1.40E+02 <2.15 >99.9999% >6.32 75% 1.40E+02 <2.15 >99.9999% >6.32 50% 1.40E+02 <2.15 >99.9999% >6.32 Table 8 - PN13.002 test results against Enterococcus hirae Test Microorganism Test Article Contact Time Test Concentrations Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 9.37E+07 8.37 Enterococcus faecalis (VRE) NC12201 PN13.002 10 seconds 80% 1.61E+08 8.21 31.78% 0.17 75% 1.65E+08 8.22 30.08% 0.16 50% 1.83E+08 8.26 22.46% 0.11 60 seconds 80% 2.40E+02 2.38 99.9999% 5.99 75% 3.90E+03 3.59 99.998% 4.78 50% 3.30E+07 7.52 86.02% 0.85 600 seconds 80% 1.40E+02 <2.15 >99.9999% >6.23 75% 1.40E+02 <2.15 >99.9999% >6.23 50% 1.40E+02 <2.15 >99.9999% >6.23 Table 9 - PN13.002 test results against Enterococcus faecalis (VRE) Test Microorganism Test Article Contact Time Test Concentrations Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 9.99E+07 8.99 Staphylococcus aureus (MRSA) NC 14402 PN13.002 10 seconds 80% 6.65E+07 7.82 93.14% 1.16 75% 8.65E+07 7.94 91.08% 1.05 50% 9.90E+07 8.00 89.79% 0.99 60 seconds 80% 3.35E+06 6.53 99.65% 2.46 75% 1.13E+07 7.05 98.84% 1.94 50% 1.41E+07 7.15 98.55% 1.84 600 seconds 80% 1.40E+02 <2.15 >99.9999% >6.23 75% 1.40E+02 <2.15 >99.9999% >6.23 50% 1.40E+02 <2.15 >99.9999% >6.23 Table 10 - PN13.002 test results against Staphylococcus aureus (MRSA) Test Microorganism Test Article Contact Time Test Concentrations Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 9.14E+07 8.14 Escherichia coli K12 NC 10538 PN13.002 10 seconds 80% 1.26E+07 7.10 90.94% 1.04 75% 1.48E+07 7.17 89.35% 0.97 50% 1.48E+07 7.17 89.35% 0.97 60 seconds 80% 1.40E+02 <2.15 >99.9999% >5.99 75% 1.40E+02 <2.15 >99.9999% >5.99 50% 1.40E+02 <2.15 >99.9999% >5.99 600 seconds 80% 1.40E+02 <2.15 >99.9999% >5.99 75% 1.40E+02 <2.15 >99.9999% >5.99 50% 1.40E+02 <2.15 >99.9999% >5.99 Table 11 - PN13.002 test results against Escherichia coli K12 Test Microorganism MYCOBACTERIUM Test Article PN13 Contact Time Test Concentrations Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 9.19E+07 8.19 Mycobacterium terrae ATCC 15755 PN13.003 20 minutes 80% 3.60E+07 7.56 77.09% 0.64 120 minutes 80% 3.10E+07 7.49 80.05% 0.70 65% 3.50E+07 7.54 77.61% 0.65 45% 5.60E+07 7.75 63.69% 0.44 360 minutes 80% 1.15E+07 7.06 92.59% 1.13 65% 1.65E+07 7.22 89.53% 0.98 45% 4.30E+07 7.63 72.46% 0.56 Test Culture Suspension / V Enumeration 9.19E+07 8.19 Mycobacterium terrae ATCC 15755 PN13.004 20 minutes 80% 2.25E+07 >7.35 85.55% 0.84 65% 2.70E+07 7.43 82.62% 0.76 120 minutes 80% 1.40E+02 <2.15 >99.9999% >6.04 65% 4.70E+05 5.67 99.69% 2.52 45% 8.15E+07 7.91 47.52% 0.28 360 minutes 80% 1.40E+02 <2.15 >99.9999% >6.04 65% 1.40E+02 <2.15 >99.9999% >6.04 45% 1.85E+07 7.27 87.98% 0.92 Table 12 - PN13.003 and PN13.004 test results against Mycobacterium terrae Test Microorganism FUNGUS Test Article PN13 Contact Time Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 7.49E+06 6.46 Candida albicans ATCC 10231 PN13.005 10 minutes 3.30E+03 >3.52 99.89% <2.94 18 hours 1.40E+02 <2.15 >99.995% >4.32 Test Culture Suspension / V Enumeration 7.45E+06 6.45 Aspergillus brasiliensis ATCC 16404 PN13.005 10 minutes >1.65E+04 >4.22 99.41% <2.23 18 hours 1.40E+02 <2.15 >99.995% >4.32 Test Culture Suspension / V Enumeration 7.57E+06 6.57 Mucor circinelloides NCPF 2708 PN13.005 10 minutes >1.65E+04 >4.22 99.56% <2.35 18 hours 4.10E+02 2.61 99.989% 3.96 Table 13 - PN13.005 test results against Candida albicans, Aspergillus brasiliensis and Mucor circinelloides Test Microorganism BACTERIA Test Article PN13 Contact Time Test Concentrations (%) Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 8.51E+07 7.51 Methicillin-resistant Staphylococcus aureus Nc14402 PN13.005 10 minutes 100 1.40E+02 <2.15 >99.999% >5.37 75 1.40E+02 <2.15 >99.999% >5.37 18 hours 100 1.40E+02 <2.15 >99.999% >5.37 75 1.40E+02 <2.15 >99.999% >5.37 Test Culture Suspension N Enumeration 8.68E+07 7.68 Enterococcus faecalis (VRE) NC12201 PN13.005 10 minutes 100 1.40E+02 <2.15 >99.999% >5.53 75 1.40E+02 <2.15 >99.999% >5.53 18 hours 100 1.40E+02 <2.15 >99.999% >5.53 75 1.40E+02 <2.15 >99.999% >5.53 Test Culture Suspension N Enumeration 8.51E+07 7.51 Escherichia coli ATCC 10538 PN13.005 10 minutes 100 1.40E+02 <2.15 >99.999% >5.37 75 1.40E+02 <2.15 >99.999% >5.37 18 hours 100 1.40E+02 <2.15 >99.999% >5.37 75 1.40E+02 <2.15 >99.999% >5.37 Table 14 - PN13.005 test results against Methicillin-resistant Staphylococcus aureus, Enterococcus faecalis (VRE) and Escherichia coli Test Microorganism VIRUS Test Article PN13 Contact Time Test Concentrations Average Log of TCID50 / ml Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 7.50 Influenza A H1N1 A / PR / 8 / 34 PN13.005 10 minutes 100 2.50 99.999% 5.00 75 3.67 99.985% 3.83 50 5.83 97.86% 1.67 18 hours 100 2.50 99.999% 5.00 75 3.00 99.997% 4.50 50 4.83 99.787% 2.67 Test Culture Suspension N Enumeration 6.50 Human Coronavirus 229E PN13.005 10 minutes 100 2.50 99.99% 4.00 75 4.33 99.32% 2.17 50 5.00 96.84% 1.50 18 hours 100 2.50 99.99% 4.00 75 2.83 99.98% 3.67 50 5.17 95.32% 1.33 Table 15 - PN13.005 test results against Influenza A and Human Coronavirus Test Microorganism Test Article PN13 Contact Time Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero BACTERIA Methicillin-resistant Staphylococcus aureus ATCC 33591 Test Culture Suspension N Enumeration 1.79E+07 7.25 - - PN13.007 80% 30 minutes ±30 secs <5.08E+01 <1.71 >99.9997 % >5.54 3 hours ±5 mins <5.08E+01 <1.71 >99.9997 % >5.54 PN13.007 60% 30 minutes ±30 sec <5.08E+01 <1.71 >99.9997 % >5.54 3 hours ±5 mins <5.08E+01 <1.71 >99.9997 % >5.54 PN13.007 40% 30 minutes ±30 sec <5.08E+01 <1.71 >99.9997 % >5.54 3 hours ±5 mins <5.08E+01 <1.71 >99.9997 % >5.54 FUNGUS Mucor circinelloides ATCC 24905 Test Culture Suspension N Enumeration 1.12E+07 7.05 - - PN13.007 80% 30 minutes ± 30 secs <5.08E+01 <1.71 >99.9995 % >5.34 3 hours ±5 mins <5.08E+01 <1.71 >99.9995 % >5.34 PN13.007 60% 30 minutes ± 30 secs <5.08E+01 <1.71 >99.9995 % >5.34 3 hours ±5 mins <5.08E+01 <1.71 >99.9995 % >5.34 PN13.007 40% 30 minutes ± 30 secs <5.08E+01 <1.71 >99.9995 % >5.34 3 hours ±5 mins <5.08E+01 <1.71 >99.9995 % >5.34 Table 16 - PN13.007 test results against Methicillin-resistant Staphylococcus aureus and Mucor circinelloides For Table 16 above, a bespoke study protocol RG220013A was used - in vitro quantitative suspension test for the evaluation of fungicidal / bactericidal activity. Note that the lower limit of detection for this study was 5.08 x 101 CFU / ml and is noted as <5.08E+01 CFU / ml in Table 16. Test Microorganism BACTERIA Test Article Contact Time Test Concentrations (%) Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 8.56E+07 7.56 Methicillin-resistant Staphylococcus aureus NCTC 12493 PN13.008 3 hours 100 C1.40E+02 <2.15 99.99996% >6.41 20 C1.40E+02 <2.15 99.99996% >6.41 2 C1.40E+02 <2.15 99.99996% >6.41 Table 17 - PN13.008 test results against Methicillin-resistant Staphylococcus aureus 10 Test Microorganism BACTERIA Test Article Contact Time Test Concentrations (%) Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero Test Culture Suspension N Enumeration 8.57E+07 7.57 Methicillin-resistant Staphylococc us aureus NCTC 12493 PN13.016 3 hours 80 8.15E+05 5.91 97.81% 1.66 40 7.10E+07 7.85 No Reduction -0.28 8 2.43E+07 7.39 No Reduction -0.19 PN13.017 (Negative control -potassium iodide (KI) 3 hours 80 7.50E+07 7.88 No Reduction -0.41 40 6.70E+07 7.83 No Reduction -0.26 8 6.70E+07 7.83 No Reduction -0.26 PN13.018 3 hours 80 <140 <2.15 99.9996% >5.42 40 8.00E+02 2.90 99.998% 4.67 8 8.80E+07 7.94 No Reduction -0.37 PN13.013 3 hours 80 n / a n / a 99.99992% >6.09 PN13.014 3 hours 80 n / a n / a 99.999% 4.91 PN13.015 3 hours 80 n / a n / a 99.99992% >6.09 Test Culture Suspension / V Enumeration 8.72E+07 7.72 Methicillin-resistant Staphylococc us aureus NCTC 12493 PN13.019 3 minutes 80 9.10E+02 2.96 99.998% 4.76 30 minutes 80 <1.40E+02 <2.15 >99.999% >5.57 PN13.020 3 minutes 80 4.45E+07 7.65 16.037% 0.07 30 minutes 80 7.80E+02 2.89 99.999% 4.83 PN13.021 3 minutes 80 1.27+04 4.10 99.976% 3.62 30 minutes 80 <1.40E+02 <2.15 >99.999% >5.57 Table 18-PN13.013, PN13.014, PN13.015, PN13.016, PN13.017, PN13.018, PN13.019, PN13.020 and PN13.021 test results against Methicillin-resistant Staphylococcus aureus Some efficacy tests in Table 18 were undertaken to investigate whether any log reduction was attributable to the excipients used. The levels of these excipients in PN13 do not contribute to the efficacy of the product. Note that: Test articles PN13.008 and PN13.013 are comprised of ascorbic acid only, with 5 a pH range of <4. Test article PN 13.014 was dehydroascorbic acid, not buffered. Test article PN13.016 was ascorbic acid and sodium bicarbonate with a pH of 5.3. Test article PN 13.017 was Potassium Iodide, which was being used as a 10 negative control for the purposes of evaluating iodide in other test articles. No data is available for ‘average CFU / ml’ and ‘log™ recovered’ for PN 13.013, PN 13.014 and PN 13.015 in this table 18. The relevant results are from a failed validation test. Test Microorganism Test Article PN13 Contact Time Average CFU / ml Logio Recovered Percentage Reduction Compared to Control at Time Zero Logio Reduction Compared to Control at Time Zero - Inert Control Time Xero (Pre-Test) 7.74E+06 6.89 - - BACTERIA Methicillin-resistant Staphylococcus aureus ATCC 33591 PN13.006 30 minutes ±30 sec <5.00E+01 <1.70 >99.9994% >5.19 3 hours ±5 mins <5.00E+01 <1.70 >99.9994% >5.19 - Inert Control Time Xero (Post-Test) 1.88E+07 7.28 - - - Inert Control Time Xero (Pre-Test) 3.21E+06 6.51 - - FUNGUS Mucor circinelloides ATCC 24905 PN13.006 3 minutes ± 2 sec 3.18 E+06 6.50 2.28% 0.01 30 minutes ± 30 sec 9.75E+05 5.99 69.8% 0.52 3 hours ±5 mins <5.00E+01 <1.70 >99.998% >4.81 - Inert Control Time Xero (Post-Test) 2.93E+06 6.47 - - Table 19 - PN13.006 test results for topical delivery route against Methicillin-resistant Staphylococcus aureus and Mucor circinelloides Note that the lower limit of detection for this study was 50 CFU / ml, which is noted as <5.00E+01 CFU / ml in the table above. This study involved In Vitro Suspension Time 5 Kill methodology. The examples and embodiments described above are provided by way of example only, and various changes and modifications will be apparent to persons skilled in the art without departing from the scope of the present invention as defined by the 10 appended claims.

Claims

1. A pharmaceutical composition or formulation for use as an active ingredient of a medicament or for use as an active ingredient in therapy, comprising:at least 1 milligram of iodide (I-);any one or more of the group comprising: an ascorbic acid, a dehydroascorbic acid, or a pharmaceutically acceptable ascorbate or salt of any of the group; andpharmaceutical-grade water;in which the composition or formulation is provided as a first portion having a pH for storage which is in the range pH 1 to pH 3, and the composition or formulation substantially lacks Na+ or K+.

2. A composition or formulation as claimed in claim 1, comprising a pH adjuster or pH-adjusting excipient in a second portion, the pH adjuster or pH-adjusting excipient being or including diethanolamine.

3. A composition or formulation as claimed in claim 1 or claim 2, in which:the iodide is up to 10% by mass of the composition or formulation;the group constitutes the same percentage mass as the iodide, or a lower or higher percentage mass than the iodide;when dependent on claim 2, the diethanolamine is up to 10% by mass of the composition or formulation; andthe pharmaceutical-grade water makes up most or all of the remaining percentage mass of the composition or formulation.

4. A composition or formulation as claimed in claim 2, or claim 3 when dependent on claim 2, in which the iodide, the group and a first amount of the pharmaceutical-grade water are provided as a major aqueous portion which is the first portion of the composition or formulation, and the diethanolamine and a second amount of the pharmaceutical-grade water are provided as a minor aqueous portion which is the second portion of the composition or formulation.

5. A composition or formulation as claimed in any of claims 1 to 4, in which the iodide is free iodide and the composition or formulation substantially lacks free metal cations.

6. A composition or formulation as claimed in claim 2, or any of claims 3 to 6 when dependent on claim 2, in which the pH adjuster does not comprise any one ormore of: sodium bicarbonate, sodium hydroxide, potassium bicarbonate, potassium hydroxide.

7. A composition or formulation as claimed in any preceding claim, in whichthe molar concentration of iodide (I-) is up to around 0.5 or 1.0 mol dm-3, or is in the range 0.0009 mol dm-3 to 0.35 mol dm-3; and / orthe amount of iodide is in the range substantially 0.12 mg / ml to substantially 150 mg / ml, or in the range substantially 0.5 mg / ml to substantially 100 mg / ml.

8. A composition or formulation as claimed in any preceding claim, comprising any one, some or all of the following:the total mass of ascorbic group moieties is at least half of the mass of iodide;the pharmaceutical-grade water is between about 12 times to about 4000 times the mass of iodide; andthe composition or formulation has an osmolarity of 200 to 500 mOsmol / L.

9. A composition or formulation as claimed in any preceding claim, comprising a pharmaceutically acceptable diluent, excipient or carrier.

10. A composition or formulation as claimed in any preceding claim, for use as one of:i) an injectable medicament, an intravenous medicament, a subcutaneous medicament, or an intramuscular medicament; orii) a topical medicament.

11. A composition or formulation as claimed in any preceding claim, for use in treating a condition, disease or infection caused by or resulting from any one or more of a pathogen, a multi drug resistant pathogen or a multi antibiotic resistant bacterium.

12. A composition or formulation as claimed in any preceding claim, for use in treating a condition, disease or infection caused by or resulting from a pathogen selected from the group consisting of: Clostridium difficile’, Acinetobacter baumannii (beta-lactam resistant); Pseudomonas aeruginosa’, Pseudomonas aeruginosa (beta-lactam resistant); Cryptococcus gattif, Candida auris’, Aspergillus fumigatus’, Enterobacteriaceae’, Enterobacteriaceae (ESBL-producing E.coli); Enterococcus faeciunr, Enterococcus faecium (vancomycin resistant); Staphylococcus aureus, Staphylococcus aureus (methicillin resistant); Neisseria gonorrhoeas, Neisseria gonorrhoeae (tetracycline resistant); Influenza; Human Coronavirus; Mucor, Mucor circinelloides’, Klebsiella pneumoniae’, Candida albicans’, Candida albicans (multi drug resistant); Enterococcus hirae’, Enterococcus faecalis (VRE); Escherichia coir, Mycobacterium terrae.

13. A kit, container, container with a syringe-compatible seal, inhaler, nebuliser, patch, dressing, damp / wet dressing, bandage, damp / wet bandage, fabric, damp / wet fabric, or syringe comprising pharmaceutical composition or formulation according to any preceding claim.

14. A method of manufacturing a pharmaceutical composition or formulation, comprising the steps of:a) generating, substantially in the absence of Na+ or K+, at least 1 milligram of iodide (I-) by reducing or reacting iodine (I2) with an ascorbic acid or a pharmaceutically acceptable salt of the ascorbic acid, providing a first portion having a pH for storage which is in the range pH 1 to pH 3 and which substantially lacks Na+ or K+; andb) packaging the first portion of the pharmaceutical composition or formulation.

15. A method as claimed in claim 14, in which the mixing in step (a) includes an amount of pharmaceutical-grade water, and a weight ratio of 1 part ascorbic acid or pharmaceutically acceptable salt thereof to 1.5 to 1.6 parts iodine to 18 to 20 parts pharmaceutical-grade water.

16. A method as claimed in claim 14 or claim 15, including packaging a second portion of the composition or formulation comprising a pH adjuster or pH-adjusting excipient in a secondary package or compartment.

17. A method of preparing a medicament, comprising the steps of:a) providing a pharmaceutical composition or formulation which comprises at least 1 milligram of iodide (I-) and an amount of any one or more of the group comprising an ascorbic acid, a dehydroascorbic acid or a pharmaceutically acceptable salt of any of the group, in which thepharmaceutical composition or formulation is provided as a first portion having a pH for storage which is in the range pH 1 to pH 3; andb) adding a pH adjuster or pH-adjusting excipient to the pharmaceutical composition or formulation to provide the medicament.

18. A method as claimed in claim 17, in which the volume of pH adjuster is less than the volume of the pharmaceutical composition or formulation.

19. A method as claimed in claim 17 or claim 18, in which the pH adjuster is alkaline or has a pH in the range pH 10 to pH 12, and in which the resulting medicament is acidic.

20. A method as claimed in any of claims 17 to 19, comprising:i) the pharmaceutical composition or formulation is provided in an infusion bag prior to or during step (a), and / or the medicament is put into an infusion bag during or after step (b); orii) the pharmaceutical composition or formulation is provided in a syringe or vial prior to or during step (a), and / or the medicament is put into a syringe during or after step (b); oriii) the pharmaceutical composition or formulation is provided in a container prior to or during step (a), and / or the medicament is put into a container during or after step (b); oriv) the pharmaceutical composition or formulation is provided in a transdermal patch or dressing or bandage or fabric prior to or during step (a), and / or the medicament is put into a transdermal patch or dressing or bandage or fabric during or after step (b).

21. A method as claimed in any of claims 14 to 20, in which the pharmaceutical composition or formulation is as claimed in any of claims 1 to 12, and / or in which the pH adjuster or pH-adjusting excipient is diethanolamine.

22. Use of an ascorbic acid or a pharmaceutically acceptable salt of the ascorbic acid to generate iodide (I-) from iodine (I2) in manufacture of a first portion of a pharmaceutical composition or formulation for use as a medicament or for usein therapy, the first portion having a pH for storage which is in the range pH 1 to pH 3 and which substantially lacks Na+ or K+.

23. Use of diethanolamine as a pH adjuster and / or as an excipient in a composition or formulation comprising iodide (I-) and any one or more of the group comprising an ascorbic acid, a dehydroascorbic acid, or a pharmaceutically acceptable ascorbate or salt of any of the group, in preparation of a pharmaceutical composition or formulation for use as a medicament or for use in therapy.

24. An ex vivo method of preparing or protecting any one or more of an organ, a tissue, bodily fluid, blood and / or plasma for transport or transplant or transfusion or storage, the method comprising at least one of:a) injecting or infusing or applying a pharmaceutical composition or formulation according to any of claims 1 to 12 to the organ or tissue or bodily fluid ex vivo,b) immersing or coating or washing or cleaning the organ or tissue or bodily fluid or blood or plasma, using a pharmaceutical composition or formulation (or solution or flush thereof) according to any of claims 1 to 12.

25. A container of ex vivo blood or plasma or an ex vivo tissue or ex vivo organ, comprising the pharmaceutical composition / formulation of any of claims 1 to 12.T +44(0)30 0300 2000A

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