Synergistic antimicrobial preparations containing chlorite and hydrogen peroxide

Abstract

An anti-microbial preservative for use in ophthalmic and dermatologic products. The preservative includes from about 0.005 wt. % to about 0.20 wt. % chlorite compound and from about 0.005 wt. % to about 0.05 wt. % peroxy compound. Additionally, the preservative does not generate chlorine dioxide within the pH range of 5.0-8.8. Also included are an antimicrobial ophthalmic and dermatologic compositions for direct application onto an eye or skin of a living being including from about 0.005 wt. % to about 0.20 wt. % chlorite compound and from about 0.005 wt. % to about 0.05 wt. % peroxy compound. Also included are methods for treating dryness of the eyes and skin disorders (e.g., wounds, burns, infections, ulcerations, psoriasis, etc.) and for disinfecting and cleansing contact lenses while in place upon an eye by applying the composition to the eye or to the contact lens.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present invention is a continuation-in-part of U.S. patent application Ser. No. 10 / 614,646 filed on Jul. 7, 2003, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 911,638 filed Jul. 23, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 412,174 filed Oct. 4, 1999, the entirety of the disclosures of which are expressly incorporated herein by reference. STATEMENT RE: FEDERALLY SPONSORED RESEARCH / DEVELOPMENT [0002] Not ApplicableBACKGROUND [0003] 1. Field of the Invention [0004] The present invention relates generally 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 for application to body parts, iii) to prevent or deter scar formation; iv) to treat dermatological disorders such as wounds, burns, ulcers, psoriasi...

AI Technical Summary

Benefits of technology

[0045] The present invention provides antimicrobial preparations (e.g., solutions, gels, ointments, creams, etc.) for disinfection of articles or surfaces (e.g., contact lenses, counter tops, etc.), antisepsis of skin or other body parts, prevention or minimization of scarring, and / or treatment or prophylaxis of dermal (i.e., skin or mucous membrane) disorders (e.g., wounds, burns, infections, cold sores, ulcerations, psoriasis, scar forming lesions, acne), and the treatment of ophthalmic disorders (e.g., infection, inflammation, dry eye, allergic conjunctivitis, and wound healing). The antimicrobial preparations of this invention generally comprise from about 0.001% to about 0.20% by weight of a metal chlorite in combination with from 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 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. Moreover, when applied or administered to treat derial disorders (e.g., wounds, burns, infections, ulcerations, acne and psoriasis), the chlorite / peroxide preparations of the present invention will not only prevent or lessen microbial infection, but will additionally provide oxygen to the affected tissue, assist in healing and deter scar formation.

[0048] Further in accordance with the invention, there are provided methods for deterring scar formation by application or administration of a chlorite / peroxide preparation of the present invention.

Problems solved by technology

Thus, chlorite has not been routinely used as an active microbicidal ingredient in preparations for topical application to the skin.

Concentrated chlorine dioxide in its liquid or gaseous state is highly explosive and poisonous.

For this reason, it is generally not feasible to dispense pure chlorine dioxide for use as a topical antimicrobial agent or disinfectant.

Drawbacks or problems associated with these prior chlorine dioxide generating systems include a) the inconvenience of handing two separate containers or chemical components, b) the difficulty of delivering such two-component systems to the intended site of application, and c) the fact that these prior systems are of acid, rather than neutral, pH.

Moreover, the prior chlorine dioxide generating systems which utilize acid-induced generation of chlorine dioxide can, if uncontrolled, cause the generation of chlorine dioxide to occur quite rapidly and, as a result, the disinfectant or antimicrobial potency of the solution may be short lived.

Increasing the concentration of chlorite and acid within the solution may prolong its disinfectant or antimicrobial shelf life, but such increased concentrations of these chemicals can result in toxicities or (in topical applications) skin irritation.

Such increased concentrations may also result in the generation of more chlorine dioxide than is required.

However, long term storage and stability are issues with the aqueous solutions described in the above-identified Laso patent, because such mixtures tend to generate chlorine dioxide very quickly, thus diminishing the long term stability of such mixtures.

McNicholas et al., states that temperatures “much below” 70 degrees C. are ineffective to drive off the free peroxide in the solution and that temperatures should not exceed 92 degrees C. because at higher temperatures the chlorine dioxide will be driven off.

While antibiotics may provide an effective form of treatment, several dangers are often associated with the use of antibiotics in the clinical environment.

These dangers may include but are not limited to: (1) changes in the normal flora of the body, with resulting “superinfection” due to overgrowth of antibiotic resistant organisms; (2) direct antibiotic toxicity, particularly with prolonged use which can result in damage to kidneys, liver and neural tissue depending upon the type of antibiotic; (3) development of antibiotic resistant microbial populations which defy further treatment by antibiotics.

While even minor wounds and abscesses can 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 treatment.

Once something triggers a person's genetic tendency to develop psoriasis, it is thought that in turn, the immune system triggers the excessive skin cell reproduction.

However, the effectiveness of the currently accepted treatments for psoriasis is subject to considerable individual variation.

The unrelieved pressure, along with numerous contributing factors, leads to the skin breakdown and persistent ulcerations.

Over time, the weight of this column of blood causes fluid and protein to exude into surrounding tissues, resulting in swollen, hyperpigmented ankles, tissue breakdown, and ulceration.

Arterial ulcers, caused by trauma to an ischemic limb, can be very painful.

However, most diabetic ulcers result from diabetic neuropathy—because the patient cannot feel pain in his foot, he is unaware of injuries, pressure from too-tight shoes, or repetitive stress that can lead to skin breakdown.

During lens wear mucus material, lipids and proteins accumulate on contact lenses, making lens wear uncomfortable due to irritation, burning sensation, and redness.

Dry eye is a syndrome in which tear production is inadequate or tear composition is inappropriate to properly wet the cornea and conjunctiva.

In most instances, the tear film loses its normal continuity and breaks up rapidly so that it cannot maintain its structure during the interval between spontaneous blinks.

Untreated dry eye can be further deteriorated to produce more severe epithelial erosion, strands of epithelial cells, and local dry spots on the cornea, which can be further complicated by microbial infection.

Statistical investigation indicates that about 30 of every 100,000 contact lens wearers develop ulcerative keratitis annually in the United States, thus making the disease a significant public health issue in view of potential blindness that can occur.

While eyelids, blinking of the eyelids, and corneal and conjunctival epithelial cells provide barriers to microbial invasion, one or more of these defense mechanisms can become compromised.

Such compromises can include lid abnormalities, exposure of the corneal surface, poor tear production, epithelial problems, medication toxicity, trauma, and incisional surgery.

This organism produces destructive enzymes, such as protease, lipase, and elastase, and exotoxins, which result in necrotic ulceration and perforation.

Once this attachment has occurred, the destructive process of inflammation, necrosis, and angiogenesis can ensue.

While such antibiotics are in wide spread use, they can also become misused where antibiotic resistant pathogens emerge.

Additionally, antibiotics only halt the proliferation of bacteria, but do not inhibit the activity of protease enzymes, endotoxins, or exotoxins.

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