Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice
Reexamination Certificate
1998-11-30
2001-07-17
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Cosmetic, antiperspirant, dentifrice
C424S078070, C424S443000, C424S667000, C514S772200, C514S772300, C514S781000, C514S782000, C514S784000, C514S928000
Reexamination Certificate
active
06261577
ABSTRACT:
FIELD
This application describes a method of topically treating skin with iodine to kill pathogens in and on the epidermal surface of the skin without irritating the skin and without leaving a visable skin discoloration and to non-staining topical iodine compositions that provide antimicrobial persistence for the disinfection of topical pathogens and for treatment and/or prevention of skin infections and diseases.
BACKGROUND OF INVENTION
Tincture of iodine was first used as a topical disinfectant in 1839. Tincture of iodine and subsequent iodine compositions, like Lugol's solution, are topical irritants that stain human skin. The invention of povidone iodine in 1956 (U.S. Pat. No. 2,739,922), commonly referred to as “tamed” iodine, eliminated the topical irritancy associated with iodine but not the staining.
Povidone iodine contains very low (1-10 ppm) concentrations of molecular iodine (I
2
) and high concentrations of triiodide (I
3
−
≈10,000 ppm) and iodide (I
−
≈5,000 ppm). Such compositions are referred to as “complexed” iodine. Complexed iodine generically refers to compositions wherein molecular iodine is complexed with organic molecules and/or iodide. Molecular iodine is complexed in order to increase shelf-life and reduce irritation. It is currently described in the literature and believed by those skilled in the art that molecular iodine is the iodine species responsible for epidermal irritancy and staining. By lowering the concentration of molecular iodine it is believed that the irritancy and staining of iodine is minimized.
Many inventions that rely upon complexed iodine have been made in the field of topical iodine compositions. Iodine is complexed by contacting a source of diatomic iodine (I
2
) with a polymeric material having large segments of polymeric residues derived from ethylene oxide, propylene oxide or other alkylene oxides in the form of block polymer chains. Examples include ethoxylated surfactants, cellulose, cellulose derivatives and polyvinyl pyrrolidone components. The alkoxylated (usually ethoxylated) surfactants include, but are not limited to, the group consisting of alkylphenol ethoxylates, ethoxylated fatty acids, alcohol ethoxylates, alcohol alkoxylates, polysorbates (ethoxylated sorbitol) and ethylene oxide-propylene oxide copolymers (commonly called Poloxamers as described in U.S. Pat. No. 5,368,868). A preferred source of iodine for reaction with nonionic materials to form iodine complexes is a composition comprising iodine in association with an inorganic iodide which provides a source of “active” iodine. Such a source is described in Winicov, U.S. Pat. No. 3,028,299, Cantor et. al. U.S. Pat. No. 3,728,449, Schmidt W. et. al. U.S. Pat. No. 5,503,838, Brink et al. U.S. Pat. No. 5,173,291, and McKinzie M. et al., U.S. Pat. No. 5,529,770. Commonly, at least 0.35 parts of iodide (I
−
) are present per part of diatomic iodine.
Topical application of biocidal agents has been accomplished using solutions, ointments and physical appliances. To provide prolonged antisepsis, it is usually necessary to repeatedly apply an iodine topical agent since microorganisms may survive the initial application. Topical iodine biocides are usually water soluble which leads to their removal from the epidermis by contact with water or bodily fluids. Increasing the water and bodily fluid resistance of topically applied iodine agents and thereby increasing the substantivity and length of bactericidal activity has been a long-standing goal in the art. This invention teaches against compositions that impart a highly visible iodine coloration to the epidermis such as that derived from complexed iodine and further discloses formulation constraints to provide a persistent non-irritating topical iodine disinfectant that does not stain. Such compositions have several commercially useful properties. The iodine compositions of this invention are not materially affected by water and body fluids and provide long lasting efficacy. Also, the compositions of this application provide iodine in a form that is capable of penetrating the skin and inactivating pathogens that reside within and on the skin.
SUMMARY OF THE INVENTION
The term “molecular iodine” as used herein refers to diatomic iodine, which is represented by the chemical symbol I
2
, which is not complexed with other molecules so that it is free to diffuse into epidermal tissue.
The term “complexed iodine” as used herein, refers to free molecular iodine that is combined with an organic carrier or with iodide anions to form triiodide such that the chemical activity of free molecular iodine is reduced. The complexed iodine is preferably prepared by combining diatomic iodine and a complexing agent.
The term “iodide anion” as used herein, refers to the species that is represented by the chemical symbol I
−
. Suitable counter-ions for the iodide anion include sodium potassium and the like.
The term “triiodide” as used herein, refers to the species which is represented by the chemical symbol I
3
−
. It is recognized by one skilled in the art that triiodide can dissociate into one iodide anion and one molecule of free molecular iodine.
The term “total iodine” as used herein, refers to the following iodine species: free molecular iodine, iodide, organically complexed forms of iodine and triiodide.
The term “rate of iodine generation” as used herein, refers to the rate at which molecular iodine is formed.
The term “ratio of molecular iodine” as used herein, refers to the ratio of molecular iodine (I
2
) to other iodine species such as iodide and triiodide.
It has been believed that molecular iodine is an irritant and responsible for the staining of skin associated with the use of topical iodine compositions. We have observed that complexed iodine, not molecular iodine, is the species of iodine that is primarily responsible for skin staining in commercially available iodine compositions. We have further observed that it is possible to formulate compositions that will deliver molecular iodine into the epidermis and not stain or irritate skin. Once molecular iodine penetrates into the skin, it maintains its biocidal activity while in the skin and can diffuse back out of the skin (W. Gottardi,
Journal of Hospital Infection,
Vol. 29, page 9, 1995). Such back-diffusion provides a long-lived chemical barrier that is resistant to water and body fluids.
This application describes the formulation constraints necessary to provide a topical iodine disinfectant that will not irritate or stain epidermal tissue but will otherwise kill pathogens on the epidermis; these formulation constraints apply to the following forms of iodine: molecular iodine, iodide, triiodide and complexed iodine. The teachings and examples in this application do not make any attempt to specifically enumerate all of the prior art in the area of topical iodine preparations. Excipients that are known to be compatible with complexed iodine may also be of use with compositions and conditions described in this application. Such excipients include surfactants, thickeners, film forming agents, penetrants, humectants, emollients, dyes, skin conditioning agents, stabilizing agents, opacifiers, wetting agents, chelating agents, buffers, organic acids and fragrances.
DESCRIPTION
Topical disinfectants are used to inactivate pathogenic organisms that are present on the epidermis and to prevent pathogenic organisms from populating the epidermis. A preferred topical disinfectant will (a) not irritate or stain the epidermis, (b) have a broad spectrum of activity, (c) rapidly inactivate pathogens, (d) provide residual activity for 2 to 8 hours, (e) resist water and bodily fluids, and (f) prevent pathogenic organisms from repopulating the epidermis. To date there are no perfect topical antimicrobial compositions in commerce. The compositions described in this application are based on defined ratios of free molecular iodine to total iodine and provide, in combination with other excipients, the basis for preferred topical disinfectants.
Iodine co
Anderson Kill & Olick P.C.
Spear James M.
Symbollon Corporation
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