SYNERGIC ANTIMICROBIAL, DERMATOLOGICAL AND OPHTHALMIC PREPARATIONS CONTAINING HYDROGEN CHLORITE AND PEROXIDEFIELD OF THE INVENTION The present invention relates in general to medical compositions and methods, and more particularly to certain disinfectant / antimicrobial preparations and methods for using such preparations i) to disinfect or preserve articles or surfaces, ii) as a topical antiseptic to be applied to parts of the body, iii) to prevent or prevent the formation of scars; iv) for the treatment of dermatological disorders such as wounds, burns, ulcers, psoriasis, acne and other lesions that form scars; and v) to treat ophthalmic disorders such as ocular dryness, wound healing and allergic conjunctivitis. BACKGROUND OF THE INVENTION A. Antimicrobial Agents and Disinfectants / AntisepticsUsed for Disinfection / Antisepsis and Topical Treatment of Wounds, Burns, Abrasions and Infections. The prior art has included numerous antimicrobial agents that have been useful for disinfecting various articles and / or for topical application to a living being, for antisepsis and / or for the treatment of dermatological disorders (e.g., wounds, burns,Ref: 128645 abrasions, infections), where it is desirable to prevent or prevent microbial growth to aid healing. Such topical antimicrobial agents have contained a variety of active microbicidal ingredients such as iodine, mercurochrome, hydrogen peroxide and chlorine dioxide. i. Previous Chlorine Dioxide Preparations Chlorite, which is a precursor of chlorine dioxide, is known to be useful as a disinfectant for water and as a preservative for solutions for the care of contact lenses. However, chlorite exhibits only weak microbicidal activity in a concentration range that is acceptable and safe for topical application to the skin (e.g., 50-1000 parts per million). Thus, chlorite has not been routinely used as an active microbicidal ingredient in preparations for topical application to the skin. In view of the limited utility of chlorite as a topical antiseptic or microbicide, various compositions and methods have been proposed for the activation or intensification of the microbicidal activity of chlorite. Examples of such compositions and methods for the activation or intensification of the microbicidal activity of chlorite. Examples of such compositions and methods for activating or enhancing the microbicidal activity of chlorite are described in US Pat. Nos. 4,997,616 (describing general activation); 5,279,673 (which describes activation in acidic medium) and 5,246,662 (which describes activation with transition metals) Chlorine dioxide (C102) and "stabilized chlorine dioxide" are known to be useful as antiseptics. Chlorine is an oxidizing agent that has a strong microbicidal activity Chlorine dioxide is generally considered superior even to gaseous chlorine, in certain water treatment applications where it is used to remove algae and other organic materials and / or to remove odors Chlorine dioxide is also effective as a microbicide, for the elimination of bacteria, viruses and microbial spores.In addition to its use as a microbicide, chlorine dioxide is a highly reactive unstable radical that is useful as an oxidizing agent in a number of other chemical and biochemical applications, for example, as described in U.S. Patent No. 4,855,135, chlorine dioxide is you can use for (a) the oxidation of double bonds between two carbon atoms; (b) the oxidation of unsaturated fatty acids (lipids) through the double bonds between two carbon atoms; (c) to accelerate the hydrolysis of carboxylic anhydrides; (d) for the oxidation of aldehydes to their corresponding carboxylic acids; (e) for the oxidation of alcohols; (f) for the oxidation of amines; (g) for the oxidation of phenols, phenolic derivatives and thiophenolic compounds; (h) for the moderate oxidation of hydroquinones; (i) for the oxidation of amino acids, proteins and polyamides; (j) for the oxidation of nitrates and sulfides; and (k) for the alteration of the CHO and CH2OH radicals of the carbohydrates, to produce carboxylic functional groups. Concentrated chlorine dioxide in its liquid or gaseous state is highly explosive and poisonous. As a result, concentrated chlorine dioxide must be handled and transported with great caution. For this reason, it is generally not feasible to distribute pure chlorine dioxide for use as a topical antimicrobial agent or disinfectant. Instead, the same antimicrobial preparations or disinfectants have been formulated to provide the "acid generation" of chlorine dioxide. Such acid-generating solutions contain a metal chlorite (i.e., a precursor of the available chlorine dioxide in powder or liquid form) in combination with an acid, which will react with the chlorite to liberate chlorine dioxide. Generally, any acid can be used for the acid generation of chlorine dioxide, including strong acids such as hydrochloric acid and sulfuric acid, and relatively strong acids such as^^ ¡i ^ 3S ^ é ¿citric acid and tartaric acid. The drawbacks or problems associated with these prior art chlorine dioxide generation systems include a) the inconvenience of handling two separate containers or chemical components, b) the difficulty of distributing such two component systems to the intended site of application, and c) the fact that these prior art systems are acidic in nature, rather than having a neutral pH. In addition, chlorine dioxide generating systems of the prior art that utilize acid-induced generation of chlorine dioxide, if not controlled, can cause the generation of chlorine dioxide very rapidly and, as a consequence, the power of the chlorine dioxide. Disinfectant or antimicrobial can be short-lived. By increasing the concentration of the chlorite and the acid in the solution, it can prolong its disinfecting or antimicrobial life, but such an increase in the concentration of these chemical compounds can result in toxicity or (in topical applications) skin irritation. Such an increase in concentration can also result in the generation of more chlorine dioxide than is necessary. Several methods have been described to limit or control the rate at which chlorine dioxide is produced in "acid generation" solutions. For example, U.S. Patent No. 31,779 (Alliger) describes a germicidal composition comprising a water-soluble chlorite, such as sodium chlorite, in combination with lactic acid. The particular composition has better disinfectant properties, properties that are not achieved by using the same composition but replacing the lactic acid by other acids such as phosphoric acid, acetic acid, sorbic acid, fumaric acid, sulfamic acid, succinic acid, boric acid, acid tannic and citric acid. The germ-killing composition is produced by contacting an acidic material containing at least 15% by weight of lactic acid, with sodium chlorite in an aqueous medium, wherein the amount of lactic acid must be sufficient to lower the pH of the medium aqueous to a value less than about 7. The described methods of disinfecting and sanitarizing a germ-bearing substrate, such as the skin, include either the application of the germ-killing composition, or the application of the reactants to obtain the production in si tu of the active agent. Also, U.S. Patent No. 5,384,134 (Kross) describes the generation of acid-induced chlorine dioxide from a metal chlorite, wherein the concentration of chlorite is limited by the amount of available chlorous acid. In particular, the Kross patent describes a method for the treatment of dermal disorders wherein a first gel, comprising a metallic chlorite, is mixed with a second gel, which comprises a protic acid. The chlorite ions present in a solution such as chlorous acid, suitably comprise no more than about 15% by weight of the total chlorite ion concentration in the composition, and the mixture of the two gels, appropriately, generates chlorine dioxide by an extended period of time, up to 24 hours. Other patents prior to the proposed describe the use of "stabilized" chlorine dioxide as a mechanism for the generation of chlorine dioxide. The term "stabilized chlorine dioxide" as used herein, refers to various compositions in which chlorine dioxide is thought to be kept in solution in the form of a weak complex. The stabilization of chlorine dioxide through the use of perborates was described in US Pat. No. 2,701,781 (de Guevara). In accordance with the de Guevara patent, an antiseptic solution of stabilized chlorine dioxide can be formed from an aqueous solution of chlorine dioxide and an inorganic boron compound, where the boron compound and chlorine dioxide are present. in the solution of a weak complex. Chlorine dioxide, fixed in this stable condition, is an essential ingredientlJ of the antiseptic solution. De Guevara's patent discloses that chlorine dioxide can be introduced into the compositions by in-situ generation thereof, or can be generated externally and introduced into the solution, for example by bubbling the gaseous chlorine dioxide into the aqueous solution. Various methods can be used for the external production of chlorine dioxide, such as a reaction of sulfuric acid with potassium chlorate, or the reaction of chlorate with oxalic acid in a moist medium. Alternatively, chlorine dioxide can be generated in itself by the reaction of potassium chlorate and sulfuric acid. Note that regardless of whether chlorine dioxide is produced in itself or externally, it is essential to release chlorine dioxide from potassium chlorate, which is induced by acid. U.S. Patent No. 4,317,814 (Laso) discloses stabilized chlorine dioxide preparations for the treatment of burns in humans. Aqueous mixtures of perborate-stabilized chlorine oxides solutions, such as chlorine dioxide in combination with glycerin, are described for topical application to burned areas and can also be administered by oral application for the treatment of burns. Aqueous solutions of chlorine oxides stabilized with perborate are described as being prepared by mixing in waterA.ÜA - fa ¬the following: sodium chlorite, sodium hypochlorite, hydrochloric acid, sulfuric acid, an inorganic perborate and a peroxy compound, such as sodium perborate. Thus, solutions prepared in accordance with the Laso patent contain chlorine dioxide, hypochlorite and peroxy compounds as strong oxidizing agents and appear to utilize the acid activation of chlorine dioxide. The Laso patent states that the methods described in it result in an immediate appeasement of the pain related to the burn in many cases, that the healing is rapid and is characterized by an absence of infections or contraction, and that the scars of the burn They were smooth and looked like normal tissue, thus eliminating the need for plastic surgery in certain cases. However, long-term storage and stability are issues in the aqueous solutions described in the Laso patent, because the mixtures tend to generate chlorine dioxide very rapidly, thus decreasing the long-term stability of said mixtures. . U.S. Patent No. 3,271,242 (McNicholas et al.) Discloses stabilized chlorine dioxide solutions which are formed by the combination of gaseous chlorine dioxide with an aqueous solution containing a peroxy compound, and subsequently, i, heat the solution to a temperature that is high enough to remove all the free peroxide, but low enough to not destroy the chlorine dioxide. McNicholas et al. , establish that "very low" temperatures of 70 ° C are not effective to eliminate the free peroxide in the solution and that the temperatures should not exceed 92 ° C because at higher temperatures the chlorine dioxide will be eliminated. McNicholas also states that, although it is not "completely understood", it is thought that the heating of the solution to eliminate the free peroxide was necessary because any amount of free peroxide that remained in the solution, would act as a leaching agent to release the chlorine dioxide from the solution. ii. Preparations of Antibiotics Antibiotic compounds have also been commonly used for the therapeutic treatment of burns, wounds and skin infections. While antibiotics can provide an effective form of treatment, several hazards are often associated with the use of antibiotics in the clinical setting. These hazards may include, but are not limited to: (1) changes in the normal flora of the body, with the resulting "superinfection" caused by the overgrowth of antibiotic-resistant microorganisms; (2) direct toxicity of the antibiotic, particularly with prolonged use, which can result in damage to the kidneys, liver and tissues of the nervous system, depending on the type of antibiotic; (3) development ofpopulations of microorganisms resistant to the antibiotic that challenge additional treatments with antibiotics. B. Dermal Disorders Difficult to Treat Different from Injuries, Burns, Abrasions and Infections. While even minor injuries and abscessesmay be difficult to treat in certain patients and / or under certain conditions, there are well-known dermal disorders such as psoriasis and dermal ulcerations, which present particular challenges for successful treatments. 15 i. Psoriasis Psoriasis is a non-contagious skin disorder that commonly appears in the form of inflamed skin lesions covered with a whitish film. This is the most common type of psoriasis, called"plaque psoriasis". Psoriasis has different variations and degrees of severity. Different types of psoriasis show features such as pustule-like blisters (pustular psoriasis), severe skin peeling (erythrodermic psoriasis), spotssimilar to drops (gouty psoriasis) and inflamed lesionssmooth (reverse psoriasis). The cause of psoriasis is unknown at present, although it is generally accepted that it has a genetic component and recently it has been established that it is an autoimmune skin disorder. Approximately one in three people reports a family history of psoriasis, but there is no inheritance pattern. There are many cases in which children with no apparent family history of the disease will develop psoriasis. The presence of psoriasis in many individuals may depend on some precipitating event or "trigger factor". Examples of "trigger factors" that are believed to affect the presence of psoriasis include systemic infections such as throat infections, skin lesions (Koebner's phenomenon), vaccinations, certain medications and intramuscular injections or oral steroid medications. Once something triggers the genetic tendency of the person to develop psoriasis, it is thought that, in turn, the immune system triggers the excessive reproduction of skin cells. The skin cells are programmed to follow two possible programs: normal growth or wound healing. In a normal growth pattern, skin cells are created in the basal cell layer and then move up through the epidermis to the stratum corneum, which is the outermost layer of the skin. The dead cells are detached from the skin at approximately the same speed that new cells are produced, maintaining a balance. This normal process takes approximately 28 days from the birth of the cell to death. When the skin is injured, a wound healing program is triggered, also known as regenerative maturation. Cells are produced at a much faster rate, theoretically forreplace and repair the wound. There is also an increase in blood supply and localized inflammation. In many ways, psoriatic skin is similar to skin that heals from a wound or reacts to a stimulus such as an infection. 15 Psoriasis due to injury is characterized by cell growth in the alternative growth program. Although there is no wound in the psoriatic lesion, the skin cells (called "keratocytes") behave as if there were. Thesekeratocytes change from a normal growth program to a regenerative maturation. Cells are created and pushed to the surface in a period as short as 2 to 4 days and the skin can not shed cells quickly enough. The excess of skin cells isaccumulates and forms high and scaly lesions. The scalesWhite (called "plaque") that normally covers the lesion, are composed of dead skin cells and the redness of the lesion is caused by an increase in blood supply to the area of rapidly dividing skin cells . Although there is no known cure for psoriasis, several treatments have shown that they provide temporary relief in some patients. However, the effectiveness of currently accepted treatments for psoriasis is subject to considerable individual variations. As a result, patients and their physicians would have to experiment and / or combine therapies in order to discover the regimen that is most effective. The treatments currently available for psoriasis are often administered in stages. Stage 1 of the treatments includes a) topical medication (e.g., topical steroids, topical retinoids), b) systemic steroids, c) mineral tar, d) anthralin, e) vitamin D3 and sunbathing. Step 2 of the treatments includes a) phototherapy (e.g., ultraviolet radiation), b) phototherapy (e.g., a combination of a topical agent activated by radiation, followed by the application of radiation to activate the agent) and c) combination therapy. Stage 3 of the treatments includes a) systemic drug therapies such as methotrexate, oral retinoids and ciclosporin and b) rotational therapy. ii. Dermal Ulcerations It is known that dermal ulcerations occur as a result of pressure, attrition or primary / secondary vascular disorders. Dermal ulcerations are generally classified according to their etiology, as follows: a. Decubitus / Pressure Ulcers - A pressure ulcer or pressure ulcer is an injury caused by a constant pressure that results in damage to the underlying tissue. Decubitus ulcers usually develop over bony prominences such as the elbows or hip. Constant pressure, along with numerous contributing factors, causes the skin to break and persistent ulcerations to occur. b. Venous Ulcers - Venous ulcers may be the result of trauma or may develop after chronic venous insufficiency (CVI). In IVC, venous valves do not close completely, allowing blood flow to return from the deep venous system through the perforated veins to the superficial venous system. Over time, the weight of this blood column causes the exudation of fluid and proteins into the surrounding tissues, resulting in swelling, hyperpigmented ankles, tissue breakdown and ulcerations. Venous ulcers may be superficial or may extend deep into the muscular layer. c. Arterial Ulcers - Leg ulcers can also develop in patients with arterial insufficiency caused by arterial vessel compression or obstruction, changes in the vessel wall, or chronic vasoconstriction. Smokers face a particularly high risk of arterial diseases, because nicotine exerts a constriction of the arteries, induces the formation of deposits of atherosclerotic plaque and exacerbates inflammatory arterial diseases (Buerger's disease) and vasoconstrictor diseases (disease or Raynaud's phenomenon). Arterial ulcers, caused by traumas in an ischemic limb, can be very painful. d. Diabetic Ulcers - Arterial insufficiency may be the cause of an ulcer not healing in a patient with diabetes. However, most diabetic ulcers are the result of diabetic neuropathy (because the patient can not feel pain in his foot, does not realize the injuries, the pressure exerted by too tight shoes or repetitive stress , which can cause skin breakage There is still a need in the art for formulations and the development of new disinfectants and preparations for topical application for the treatment of dermal disorders, such as wounds, burns, abrasions, infections, ulcerations , psoriasis and acne C. Washing and Disinfecting Contact Lenses Whenever contact lenses are removed from an eye, they should be placed in a washing and disinfecting solution until they are used again. The washing and disinfecting solutions have the following functions: 1. They help to clean the lens of the ocular secretions after the lens was removed from the eye; 2. Prevent eye infections caused by bacteria that contaminate the lenses; and 3. Maintain the state of hydration in balance, which is achieved when the lenses are being used. D. Cleaning of Contact Lenses When contact lenses are worn, mucous material, lipids and proteins accumulate in them, making the use of lenses uncomfortable because of irritation, burning sensation and redness. Because of this, the vision becomes blurred. To alleviate the problem of discomfort, soft or rigid contact lenses will• I 7 should be removed from the eye, cleaned and disinfected regularly, using an enzymatic cleaner and a disinfectant solution. One of the serious complications associated with soft contact lenses may be giant papillary conjunctivitis (GPC). It is thought that the occurrence of giant papillary conjunctivitis is due to an inflammatory reaction associated with complications caused by soft contact lenses. This is almost always caused by protein deposits in the contact lenses. GPC produces symptoms ranging from asymptomatic to pruritus, edema of the upper eyelid, redness of the eye, mucoid discharge, progressive intolerance to contact lenses. The cleanser of direct application to the eye of the present invention, effectively cleanses protein deposits and maintains healthy corneal epithelial cells by keeping the corneal surface free of microbial infections, as well as by delivering molecular oxygen. In this way, it provides convenience and benefits for both soft contact lens users and users of rigid contact lenses. E. Treatment of Ophthalmic Disorders i. Ocular Dryness Ocular dryness is a syndrome in which the production of tears is inadequate or the composition of__% __ a_ ?__i_ * 2? .- i, -. *, I. _. -. & »£» »& * '¿- -;Tears are inappropriate to properly moisturize the cornea and conjunctiva. A variety of ocular tears disorders cause sensations of ocular dryness, discomfort due to the presence of a foreign object in the eyes. In most cases, the tear film loses its normal continuity and breaks very quickly, so that it can not maintain its structure during the interval of spontaneous blinking. All these lacrimal abnormalities can have multiple causes. Possibly the most common form of ocular dryness is due to a decrease in the water component in tears. Untreated eye dryness may be aggravated to produce severe epithelial erosion, strands of epithelial cells and local dry spots in the cornea, which may be further complicated by microbial infections. However, in its mild form, a sensation of dryness and irritation in the eye can be resolved with artificial tears. Thus, the artificial tears solution having a broad spectrum antimicrobial activity with lubricating properties for the cornea, can provide not only comfort, but also beneficial effects in the recovery of the damaged corneal surface. ii. Allergic conjunctivitis Allergens from the air and from theHeat? ÍtLt. . . . . «,« Jj ss -,. * &&®.hands normally produce allergic conjunctivitis caused by an IgE-mediated hypersensitivity reaction. It presents pruritus, lacrimation, dryness and sticky eyes, including inflammation of the eyelids, conjunctive hyperemia, papillary reaction, chemosin and mucoid discharge. The presence of hyaluronic acid in tears, which is included in the formulation of artificial tears, protects the corneal surface from contact with allergens. The broad spectrum antimicrobial agent of the present invention keeps the corneal surface free of bacterial infections and also maintains healthy corneal epithelial cells by supplying them with molecular oxygen. Thus, it provides beneficial effects on the eyes sensitive to allergens. BRIEF DESCRIPTION OF THE INVENTION The present invention provides antimicrobial preparations (eg, solutions, gels, ointments, creams, etc.) for the disinfection of articles or surfaces (eg, contact lenses, lids, etc.), antisepsis of the skin or other parts of the body, prevention or minimization of scarring, and / or treatment or prophylaxis of dermal disorders (ie, of the skin or mucous membranes) (eg, wounds, burns, infections, cold sores, ulcerations, psoriasis, lesions that form scars, acne) and the treatment of ophthalmic disorders (e.g., ocular dryness, allergic conjunctivitis and wound healing). The antimicrobial preparations of the present invention generally comprise from about 0.001% to about 20% by weight of a metallic chlorite in combination with an amount of 0.001% to 0.05% of a peroxy compound such as hydrogen peroxide. Additionally, the chlorite / peroxide preparations of the present invention may contain additional components such as polymeric lubricants and surfactants, and / or may be formulated in a polymeric drug delivery system or in a liposomal preparation. The chlorite / peroxide preparations of the present invention have broad antimicrobial activity, including for example activity against gram-negative and gram-positive bacteria, yeasts and fungi. In addition, when applied or administered for the treatment of dermal disorders (eg, wounds, burns, infections, ulcerations, acne and psoriasis) the chlorite / peroxide preparations of the present invention not only prevent or diminish microbial infection, but additionally They will provide oxygen to the affected tissue, help to heal and prevent the formation of scars. Further, in accordance with the present invention, methods are provided for disinfecting articles (eg, contact lenses) and methods for the treatment of dermal disorders (eg, wounds, burns, infections, ulcerations and psoriasis) by the application or administration of a chlorite / peroxide preparation of the present invention. With respect to contact lens disinfectant solutions, as well as product formulations for cleaning contact lenses in the eye without removing them, the concentration of the metal chlorite is between 0.002 and about 0.20%. In addition, the present invention includes product formulations that show efficacy in the treatment of ocular dryness, wound healing and allergic conjunctivitis. In addition, according to the present invention, methods for preventing scar formation are provided by the application or administration of a chlorite / peroxide preparation of the present invention. Other additional aspects and objects of the present invention will be apparent to those skilled in the art upon reading and understanding the following detailed description and the examples set forth therein. DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The following detailed description and examples are provided for the purposes of describing certain exemplary embodiments of the invention and it is not intended to limit the scope of the invention in any way. The present invention provides preparations containing chlorite (e.g., metal chlorite) in combination with a small amount of hydrogen peroxide, in neutral aqueous solution (pH 6.8-7.8, preferably 7.0-7.4). These preparations exhibit a synergistic antimicrobial activity, without generating chlorine dioxide during storage, thereby making the stability of these solutions acceptable for pharmaceutical use. For example, an aqueous solution containing 400 ppm of chlorite plus 100 ppm of hydrogen peroxide, remains stable beyond 18 months at room temperature and is effective to reduce the activity of Candida albicans by 1.0 log within a period of 6 hours of challenge, even though the individual components of such a solution are not effective when applied separately at the same concentrations to reduce the activity of Candida albicans. Additionally, the hydrogen peroxide present in the chlorite / peroxide solutions of the present invention readily decomposes to molecular oxygen and water upon contact with the enzymes peroxidase and catalase present in the tissues and / or some body fluids.
Such generation in si of molecular oxygen, contributes to cellular vitality and increases the healing of wounds. The chlorite / H202 solutions of the present invention are sufficiently stable to be formulated in combination with polymeric lubricants (nonionic and / or anionic, eg, HPMC, Methocel, CMC, hyaluronic acid, etc.) and / or in combination with surfactants based on block polymers (eg, pluronics). For example, a chlorite / aqueous hydrogen peroxide system can be formulated together with methocel or hyaluronic acid as a lubricant and pluronics as a surfactant, to obtain a disinfecting solution of contact lenses (viscosity up to 50 cps at 25 degrees C) in a tonicity Ophthalmically acceptable (eg, osmolarity of at least about 200 mOsmol / kg) and a buffer solution to maintain the pH of the formulation within a physiologically acceptable range. The formulation of the solution for contact lens disinfection, artificial tears solution and direct cleaning solution to the eye, contains chlorite in an amount of preferably from about 0.005 to about 0.06% weight / volume and hydrogen peroxide in an amount of about 0.002. to approximately 0.05% weight / volume. Once again, the presence of hydrogen peroxide provides the beneficial oxygen molecule to the cornea upon contact with the catalase found in tears. A. Formulations The chlorite / peroxide preparations of the present invention can be formulated in various ways, including liquid solutions, gels, ointments, creams, sprays, etc. Below are a few examples of the types of specific formulations that can be prepared in accordance with the present invention. i. Liquid Chloride / Perioxide Stable SolutionThe following Formula 1 is a presently preferred formulation of a liquid chlorite / peroxide solution of the present invention: FORMULA 1 Sodium Chlorite 0.005% - 0.10% Hydrogen Peroxide 0.005% - 0.05% Methocel A 0.05% - 0.2% Boric Acid 0.15 % Sodium Chloride 0.75% Pluronics F-68 / F-127 0.1% HCl or NaOH Adjust to pH 7.4 Purified Water cbp The volume The chlorite / peroxide solutions of the present invention, such as the solution of the aforementioned preferred formulation, can be used for a variety of medical and non-medical applications, including but not necessarily limited to: a) disinfection of articles and surfaces such as contact lenses, medical / dental instruments, caps, treatment tables, combs and brushes, etc .; antisepsis of the skin or parts of the body (eg, a disinfectant solution for hands, antiseptic facial scrubs, etc.) and b) the treatment or prophylaxis of dermal disorders (ie, of the skin or mucous membranes) such as wounds , burns, infections, ulcerations, cold sores, psoriasis, acne and c) to prevent or prevent the prevention of scars. As noted above, the chlorite / hydrogen peroxide system of the present invention is sufficiently stable to be formulated in the form of a polymer gel or in a paste form. In addition, such a polymer gel or paste formulation may contain polymers that delay or control the release of chlorite / hydrogen peroxide (e.g., a sustained release system). Such sustained-release formulations provide surprising benefits by increasing the therapeutic index, maintaining the effective concentration of chlorite / H202 for a prolonged period in the injured sites, preventing injured sites from receiving external microbial contamination by forming a seal on the injured sites, and providing molecular oxygen to the injured tissues.
Unlike conventional ointments, polymeric gel provides a dry, clean and comfortable coating on injured sites when applied.
Such gel formulations may contain polymeric drug delivery vehicles such as hydroxypropylmethylcellulose (HPMC), methylcellulose(Methocel), hydroxyethylcellulose (HEC), hyaluronic acid and carboxymethylcellulose (CMC), etc. ii. Stable Corito / Peroxide Gel The following Formula 2 is a currently preferred chlorite / peroxide formulation of the present invention: FORMULA 2 Sodium Chloride 0.02% - 0.10% Hydrogen Peroxide 0.005% - 0.05% Methocel A 2.0% Boric Acid 0.15% Sodium Chloride 0.75% Pluronics F-68 / F-127 0.1% HCl or NaOH Adjust to pH 7.4 Purified Water cbp the volume Any of the preparations of the present invention can be formulated for the sustained release of the active components, forming liposomes of the preparation in accordance with known liposome formation techniques and / or adding a pharmaceutically acceptable amount to the formulation and effective (typically 1 to 20% by weight) of a sustained release component such as a polymer matrix or one or more of the following: a cellulose ester; hydroxymethylpropylcellulose; methylhydroxyethylcellulose; hydroxypropylcellulose; hydroxyethylcellulose; carboxymethylcellulose; a salt of a cellulose ester; cellulose acetate; Hydroxypropylmethylcellulose phthalate; methacrylic acid / methyl methacrylate copolymer; methacrylic acid / ethyl acetate copolymer; polyvinyl pyrrolidone; polyvinyl alcohol; hyaluronic acid; a phospholipid; cholesterol; a phospholipid that has a neutral charge;a phospholipid that has a negative charge; dipalmitoylphosphatidylcholine; dipalmitoylphosphatidylserine; and sodium salts thereof. iii. Ophthalmic Chlorite / Peroxide SolutionStable The following Formula 3 is a currently preferred formulation of a solution for disinfecting chlorite / peroxide contact lenses, for use in cleaning contact lenses inside or outside the eye. The formulation additionally functions as a product of tears for the lubrication of dry eyes. FORMULA 3 Sodium Chlorite 0.002% - 0.20% Hydrogen Peroxide 0.005% - 0.05% Hyaluronic Acid 0.001% - 0.50% Boric Acid 0.15% Sodium Chloride 0.75% Pluronics 127 0.05% - 2.0% HCl or NaOH Adjust to pH 7.4 Purified Water cbp Volume B. Examples of Therapeutic Applications The following are specific examples of therapeutic applications of the chlorite / peroxide preparations of the present invention.i. Example 1: Treatment of Psoriasis - Without Crossing A human patient with psoriasis plaques on both arms was treated as follows: • Application twice a day to the left arm plates only, of a chlorite / peroxide solution with the following formulation: Sodium Chloride 0.06% Hydrogen Peroxide 0.01% HPMC 2.0% Boric Acid 0.15% HCl or NaOH Adjust to pH 7.4 Purified Water cbp the volume • Application twice a day to the plates of the right arm only, of a commercial cream of 0.1% triamcinolone acetonide. The psoriatic plaques treated with chlorite / peroxide in the right arm, began to become less intense in a period of 24 hours after the treatment and had disappeared substantially in a period of 3 days after the treatment began. However, psoriatic plaques treated with triamcinolone acetonide present in the left arm remained unchanged and inflamed during the two (2) week treatment period.17 -. 17 - ^^ 4¡é j? I $ e¡ji¡? J ii. Example 2: Treatment of Psoriasis - With Crossing. A human patient with psoriasis plaques present in both arms was treated for two (2) weeks, as follows: • Application twice a day to the plates of the left arm only, of a chlorite / peroxide solution with the following formulation : Sodium Chloride 0.06% Hydrogen Peroxide 0.01% HPMC 2.0% Boric Acid 0.15% HCl or NaOH Adjust to pH 7.4 Purified Water cbp the volume • Application twice a day to the plates of the right arm only, of a commercial cream of 0.1% triamcinolone acetonide. The psoriatic plaques treated with chlorite / peroxide in the right arm, began to become less intense in a period of 24 hours after the treatment and had substantially disappeared one week after the treatment began. However, the psoriatic plaques treated with triamcinolone acetonide present in the left arm remained unaltered and inflamed during the period of two (2) weeks of treatment. Beginning one day after the end of the two (2) weeks of the treatment period and continuing for a second period of two (2) weeks of treatment, the patient was treated as follows: • Application twice a day to the plates of the left arm only, of the same 0.1% triamcinolone acetonide commercial cream previously described in this example. • Application twice daily to the plates of the right arm only, of the same chlorite / sustained release peroxide gel described above in this example. Twenty-four hours after starting the second treatment period, the psoriatic lesions of the right arm began to heal. On the third day and continuing until the end of the second period of two (2) weeks of treatment, the psoriatic lesions of the right arm had substantially disappeared. iii. Example 3: Treatment of Cold Sores A patient with painful cold sores containing fluid (ie, chancre-like ulcerations) on the lips was treated twice a day by applying a chlorite / peroxide preparation prepared in accordance with the lips to the lips. Formula 1 above.
After 6 to 12 hours of the first application of the chlorite / peroxide preparation, the patient reported that the pain had subsided. Twenty-four hours after the first application of the chlorite / peroxide preparation, the fluid contained in the cold sores had substantially dissipated and the ulcerations had a dry appearance. Six days after the first application of the chlorite / peroxide preparation, the cold sores had substantially disappeared and the lips had a normal appearance, whereas cold sores of such severity typically require a period substantially greater than 6 days to disappear and heal completely. iv. Example 4: Treatment of Venous Ulcer A patient with a venous ulcer on the right leg of 3-4 cm in diameter, which had been present for 9-12 months, was treated twice daily with the ulcer, with a gauze soaked with a liquid chlorite / peroxide solution prepared in accordance with Formula 1 above. After three days of starting the treatment, the ulcer looked clean and dry. Fourteen days after starting treatment, the ulcer began to decrease in size and new and healthy tissue was observed in its periphery. At 35 days after starting the treatment, the ulcer had healed completely without scarring and the area where the ulcer had been located was free of pain. v. Example 5: Treatment of Diabetic Decubitus Ulcer. A non-ambulatory diabetic patient with decubitus ulcers on both legs and some toes, from 12 to 18 months, was treated by a daily application to the ulcers, a sterile, clean gauze, 3 times a day, saturated with a liquid chlorite / peroxide solution prepared in accordance with Formula 1 above. After 4 to 7 days of initiating the chlorite / hydrogen peroxide treatments, the ulcers began to look less inflamed, clean and dry. Approximately 7 to 10 days after starting treatment with chlorite / hydrogen peroxide, granular tissue began to form inside the ulcers. After 12 to 14 days, re-epithelialization was observed in the ulcerated areas, except for an ulcer on one toe, which was particularly severe and had deepened to the finger bone. From 30 to 45 days after the start of treatment, all the ulcers except the severe ulcer of the toe had completely closed and re-epithelialized, without the formation of irregular scars. itself, after 30 to 45 days after the start of treatment, the toe ulcer had also been substantially reduced (but not completely closed) and the patient was able to walk. The liquid and / or gel formulations of the present invention, such as formulas 1 and 2 above, can also be applied topically to prevent the formation of scars caused by wounds, burns, acne, infections, trauma, surgical incisions or any other scars injury or disorder. saw . Example 6: a. Treatment of Ocular Dryness Conditions. Several subjects with ocular dryness had pruritus and irritated eyes. In extreme cases, the subjects suffered more serious problems that could interfere with the maintenance of their health. The subjects were treated with a preferred tear product with the following formulation: Sodium chlorite 0.005% - 0.02% Hydrogen peroxide 0.01% Methylcellulose A4M 0.075% Hyaluronic acid 0.10% - 0.125% Boric acid 0.15% Sodium chloride, USP .. 0.75% Pluronic 127 0.10%? iHCl or NaOH Adjust the pH to 7.4 Purified water c.b.p. The volume The dry eyes test of subjects with a rose bengal or fluorescein stain gave a good indication with respect to the condition of the corneal epithelium, while the rose bengal staining provides a good indication of the number of cells dead epithelial cells in the cornea, as well as in the conjunctiva. Two subjects with ocular dryness were tested with pink bengal staining and quantitative staining of the cornea and conjunctiva was documented by photographs. The subjects began to apply the above-mentioned preferred tears product, at a dose of two drops three times a day. At the end of the two weeks, the two subjects were tested with rose bengal staining and the level of staining was quantitatively documented, by photographs. The results showed a reduction of 50 to 70% in the Bengal Rose stain, which clearly indicates that the preferred formulation of tears had improved the staining of the corneous and conjunctival cells. In addition to an objective determination of the health of the epithelial cells, the two subjects were subjectively tested with respect to the safety and efficacy of the. . j. -. » < ,.,, ,, i.preferred tears product. First of all, a biomicroscopy of the subjects during the 2-week treatment period showed no redness, irritation, inflammation or other signs of discomfort. Secondly, the subjects indicated that the application of the product of tears completely eliminated the symptoms of redness, itching, irritation, pain and dryness, while providing lubrication that lasted several hours. Therefore, it is evident that the tear product exhibits both safety and efficacy in the treatment of ocular dryness. As can be recognized in view of the aforementioned antimicrobial activity of such compositions, the tear product is also effective in improving the healing of wounds in the eye, for example after surgery, where bacterial infections should be avoided. Jb. Treatment of Allergic Conjunctivitis In addition to the treatment of ocular dryness with the above-mentioned preferred tears product, the product was also tested in the treatment of disorders such as allergic conjunctivitis. In particular, two subjects suffering from allergic conjunctivitis that included pruritus, irritation and constant watering, applied two drops of the product three timesSUT ^ aT a day. This dose resulted in the disappearance of the symptoms. C. Examples of Cleaning of Contact Lenses i. Example 1: Soaking, Cleaning and Disinfection The following formulation is a preferred disinfectant solution applicable to the cleaning of contact lenses by conventional soaking. Sodium Chloride 0.05% Hydrogen peroxide .. 0.01% Methylcellulose A4M 0.075% Hyaluronic acid 0.05% - 0.10% Boric acid 0.15% Pluronic 127 0.25% - 0.50% Sodium chloride USP ... 0.75% HCl or NaOH Adjust pH to 7.4 Purified water cbp the volume Six subjects who wore soft hydrophilic contact lenses, soaked the lenses in the previous disinfectant solution and then put the lenses directly into the eyes. The soaking was carried out at night or as necessary. All six subjects reported that the lenses felt very comfortable and that they experienced no adverse effects (e.g., burning sensation, itching, redness, pain). Additionally, the solution extended the comfort and cleanliness of the•! ^ - ° 8rf ~ to lenses for several weeks beyond that experienced with other commercially available disinfectant solutions. The disinfectant solution can be used with soft hydrophilic lenses with various water contents (e.g. from 38 to 75%), as well as with rigid gas permeable lenses made of silicone and acrylate. Cyclic studies of soft lenses soaked daily in the solution for 30 days showed no damage or changes in the physical and chemical characteristics of the lenses. Comfort for the eye, as noted above, is achieved by not agglutinating or accumulating the preservative in soft lenses or rigid gas-permeable lenses, while agglutination and accumulation can be found in certain formulations currently available in the trade, which cause irritation and discomfort. ii. Example 2: Cleaning During Use according to claim 20, characterized in thatThe following formulation is a preferred disinfectant solution direct application to the eye, to clean contact lenses while they are being used, introducing the solution to the eye: Sodium Chloride 0.02% Hydrogen peroxide .. 0.01% Methylcellulose A4M 0.075% Hyaluronic acid 0.075% - 0.10% Boric acid 0.15% Sodium chloride, USP .. 0.75% Pluronic 127 0.75% HCl or NaOH Adjust the pH to 7.4 Purified water cbp Volume Four subjects applied two drops of the previous solution three times a day for 30 days while using contact lenses. Examinations of all subjects showed no irritation, burning sensation, itching or adverse effects of any kind. These subjects also reported that the solution felt soft and lubricating. Two subjects participated in a comparative study where, first of all, they used ACUVUE disposable contact lenses continuously for two weeks, with occasional removal and cleaning with commercially available cleaning solutions, followed by a saline rinse. After 14 days, the lenses became gritty and uncomfortable and were discarded. Secondly, the two subjects started with new ACUVUE lenses and practiced the daily application of the solution of the present invention three times a day without removing or touching the lenses. These subjects were able to wear the lenses for three to four weeks before their replacement. Additionally, the inconvenience of cleaning the lenses out of the eyes, as well as the risk of losing the lenses, tearing or contaminating them, was completely eliminated. Therefore, it is evident that the present direct cleaning solution in the eye provides effective cleaning as well as convenience. Those skilled in the art will note that the present invention has been described with reference to certain specific examples and embodiments. However, these are not the only examples and modalities that can be practiced with the present invention. In fact, it is possible to make several modifications to the examples and embodiments described above without departing from the spirit and intended scope of the present invention, and it is intended that all these modifications be included within the scope of the following claims. It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects to which it relates.