Drug – bio-affecting and body treating compositions – Dentifrices – Ferment containing
Reexamination Certificate
1999-01-26
2003-06-10
Rose, Shep K. (Department: 1614)
Drug, bio-affecting and body treating compositions
Dentifrices
Ferment containing
C424S053000, C424S613000, C424S440000, C424S490000, C433S215000
Reexamination Certificate
active
06576227
ABSTRACT:
TECHNICAL FIELD
This present invention relates to a method for activating a peroxidase enzyme system in situ.
BACKGROUND ART
A number of naturally occurring antimicrobial systems rely upon the ability of certain oxidizing agents to disrupt metabolic processes of bacteria, fungi and viruses. Examples of such oxidizing agents include hypothiocyanite (OSCN—/HOSCN), hypochlorite (OCl—\HOCl), and hypoiodite (OI—\HOI). These agents are known to inhibit glycolysis, penetrate prokaryotic cell walls, and generally disrupt a wide variety of processes crucial to the survival of lower organisms at concentrations greater than or equal to about 100 micromoles per liter. The oxidizing agents are formed from the detoxification of hydrogen peroxide by mammalian peroxidase systems, such as those found in saliva, cervical fluid, lachrymal fluid, and leukocytes. Examples of such peroxidase system enzymes are myeloperoxidase, lactoperoxidase, and salivary peroxidase.
Attempts to exploit these natural antimicrobial systems have been directed to both the oral care field and the gastrointestinal tract. U.S. Pat. No. 4,150,113 and U.S. Pat. No. 4,178,362 (Hoogendorn, et al.) describe dentifrice compositions containing glucose oxidase that react with plaque and salivary glucose to produce low levels of hydrogen peroxide. Hydrogen peroxide production by such systems is, however, highly irregular due to the non-uniform distribution and unpredictable availability of substrate, namely glucose, in the oral cavity.
U.S. Pat. No. 4,269,822, U.S. Pat. No. 4,564,519 and U.S. Pat. No. 4,578,265 (Pellico, et al.) further describe dentifrice compositions containing an oxidoreductase enzyme and its specific substrate in an aqueous solution for the purpose of producing hydrogen peroxide or other antimicrobial oxidizing compounds such as hypothiocyanite ion. A more predictable amount of hydrogen peroxide (and subsequently hypothiocyanite ions) is produced by the compositions of Pellico et al., compared with those of the Hoogendorn references. The differences between the two compositions reflect the availability of glucose in the oral cavity as substrate for glucose oxidase.
There are, however, a number of disadvantages associated with the compositions of Pellico et al. These include: the limited rate of enzymatically-produced hydrogen peroxide that in turn produces the hypothiocyanite ion. The short duration of oral contact time, namely during toothbrushing, means that insufficient amounts of hypothiocyanite is available to effectively eliminate microbes in the oral cavity. In addition, the references utilize glucose oxidase as the oxidoreductase enzyme that in turn relies upon the availability of a sufficient concentration of glucose in solution to produce hydrogen peroxide. However, the glucose itself is a microbial substrate and is potentially cariogenic when present in an oral care product.
U.S. Pat. No. 4,564,519 describes a chewable dentifrice, such as a chewing gum or lozenge, which contains a dual enzyme system for producing hypothiocyanite ions upon being chewed or otherwise activated by the moisture in saliva. Such compositions suffer from similar drawbacks to those mentioned immediately above namely a slow rate of enzymatically-produced hydrogen peroxidase as well as a reliance on a cariogenic compound.
Other solid or chewable compositions capable of producing hydrogen peroxide or other oxidizing agents upon activation with moisture are taught in U.S. Pat. No. 4,320,116, U.S. Pat. No. 4,726,948, and U.S. Pat. No. 4,929,466. These compositions are foodstuffs intended for consumption by livestock in order to limit the growth of harmful bacterial within the animal's gastrointestinal tract. These references describe the use of various enzymatic and non-enzymatic sources for hydrogen peroxide, where the enzymatic sources are glucose oxidase/glucose and the non-enzymatic sources are sodium perborate, sodium percarbonate, and calcium peroxide. However, it is known that sodium percarbonate and potassium percarbonate have extremely alkaline pH and are thus of little use in activating the peroxidase enzymes until exposed to the acidic environment within the gastrointestinal tract. Thus, the foodstuff compositions described in the reference cannot be used as a therapeutic or otherwise peroxidase-activating effect in the oral cavity.
It would thus be advantageous to provide substantially non-cariogenic compositions capable of rapidly producing hydrogen peroxide in conditions that are suitable for peroxidase enzyme activation in the oral cavity.
It would also be advantageous to provide compositions capable of rapidly producing antimicrobial hypohalite ions within the limited contact time available in most oral hygiene procedures.
It would also be advantageous to provide compositions capable of rapidly producing antimicrobial hypohalite ions upon contact with saliva within the limited contact time available in most oral hygiene procedures.
SUMMARY
This invention satisfies the above needs. A novel oral care composition is provided.
A preferred embodiment of the invention is a non-enzymatic, water-soluble hydrogen peroxide precursor, capable of rapidly releasing an effective amount of hydrogen peroxide for activating the peroxidase system in the oral cavity, upon contact with an aqueous solution; and a pH adjusting agent capable of producing a selected pH in the aqueous solution for facilitating the rapid release of the hydrogen peroxide from the hydrogen peroxide precursor and the activation of the peroxidase enzyme in the oral cavity.
In a further embodiment of the invention, a process is provided for manufacturing an oral care product, comprising the steps of obtaining an alkali metal percarbonate; dispersing the percarbonate in a non-hygroscopic material so as to encapsulate the percarbonate; obtaining particles of percarbonate encapsulated in the non-hygroscopic material; associating the percarbonate particles with a pH adjusting agent; and formulating the particles into an oral care product.
In a further embodiment of the invention, a method is provided for activating a peroxidase system in an oral cavity of an animal, including the steps of selecting a non-enzymatic water soluble hydrogen peroxide precursor capable of rapidly releasing an effective amount of hydrogen peroxide for activating the peroxidase system in the oral cavity upon contact with an aqueous solution; mixing the precursor with a pH adjusting agent capable of producing a selected pH in the aqueous solution for facilitating the rapid release of the hydrogen peroxide from the hydrogen peroxide precursor and the activation of the peroxidase enzyme in the oral cavity; and administering to the oral cavity the precursor and pH-adjusting agent in a suitable formulation.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to oral care compositions which upon contact with an aqueous solution, are capable of rapidly activating a peroxidase enzyme so as to release hydrogen peroxide.
The concentrations of the components of the oral composition are given in molar units which denote the concentration of the component in the aqueous contact solution.
The limiting factor in all of the mammalian antimicrobial peroxidase systems is the availability of the substrate, namely hydrogen peroxide. Furthermore, the pH of the aqueous environment determines not only the effective release of hydrogen peroxide from the precursor but also the activity of the peroxidase system and the efficacy of the resulting oxidizing agents in penetrating the cell walls of microorganisms.
It is known, for example, that the non-ionized species of hypohalite ions more readily penetrates the cell walls of microorganisms then does the ionized species thereby having increased efficiency in inhibiting the metabolism of the microorganisms. The distribution of ionized versus non-ionized species (for instance HOCl, or hypochlorous acid, versus OCl—, or hypochlorite ion) is highly pH dependent.
The pH activity profiles of the peroxidase enzymes lactoperoxidase, salivary
Banner & Witcoff , Ltd.
Oraceutical Innovative Properties LLC
Rose Shep K.
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