Drug – bio-affecting and body treating compositions – Chewing gum type
Patent
1985-03-22
1987-04-21
Rose, Shep K.
Drug, bio-affecting and body treating compositions
Chewing gum type
424 49, 424 50, 424 88, 424 92, A61K 716, A61K 968, A61K 3574, A61K 3909
Patent
active
046595619
DESCRIPTION:
DESCRIPTION
The mechanism of dental plaque formation has been the subject of a number of careful studies. The surface enamel of teeth is a complex salt of calcium and phosphate called hydroxyapatite. Hydroxyapatite readily adsorbs glycoproteins. During the course of dental prophylaxis, the teeth are cleaned down to the enamel surface with abrasives. When teeth cleaned in this way are exposed to normal fluids of the oral cavity, a thin coating of adsorbed saliva, termed an "acquired pellicle", is formed first. This acquired pellicle provides the receptor sites for the first colonizers of the teeth. Hydroxyapatite beads suspended in saliva also acquire a pellicle, and are the industrial standard and experimental model for assaying bacterial adhesion (Gibbons and van Houte, 1980).
Saliva-coated spheroidal hydroxyapatite (SC-SHA) has been accepted as the industrial standard and experimental model for five major reasons: (1) Organisms with a high affinity for binding to teeth, have a high affinity for binding to SC-SHA; those with low affinity for binding to teeth, have a low affinity for binding to SC-SHA (Hillman et al., 1970); (2) Oral bacteria which specifically bind to the tongue or buccal epithelium, and do not bind to teeth, do not bind to SC-SHA either (Clark et al., 1978); (3) Among organisms that bind to teeth, the relative proportions of each species binding to teeth is similar to the proportion of those species that bind to SC-SHA (Gibbons and van Houte, 1980); (4) The selectivity of bacterial adsorption to SC-SHA parallels that observed in experiments performed directly in the mouths of humans (Clark et al., 1978); and (5) SC-SHA is recognized as possessing an additional advantage over in vivo experiments; radioactive materials can be used permitting the mechanism of adherence to be quantitated and described in physical chemical terms (Gibbons et al., 1976; Clark et al., 1978).
At least six species of bacteria are found in plaque and S. sanguis constitutes 10-50% of the organisms present. In addition to being the most numerous organism in plaque, S. sanguis also initiates plaque development. Studies of newly cleaned teeth and of newly erupted teeth of infants show that S. sanguis is the first organism to colonize these surfaces. The adherence of S. sanguis is followed by a succession of other microorganisms including Streptococcus mutans, Actinomyces sp. and various anaerobic bacteria. These bacteria use already formed S. sanguis plaque or the by-products of the plaque for their receptor sites. Applicants have found that S. sanguis binds first by binding to its receptor sites on the salivary pellicle and that then other microorganisms bind to the receptor sites provided on S. sanguis.
S. mutans attaches to the salivary pellicle only in low numbers and in a nonspecific manner. This is shown by reference to the kinetic analyses given in FIG. 1.
FIG. 1 shows Langmuir adsorption isotherms as kinetic analyses of attachment of S. mutans cells to saliva-coated hydroxyapatite, curve (o), and to saliva-coated hydroxyapatite that contains bound S. sanguis cells, curve (.). Data for these isotherms were obtained by the following procedure:
Broth grown log phase cells were labeled with .sup.3 H-thymidine in TH broth. Washed, labeled cells suspended in phosphate buffer (pH 6.0) were added at various concentrations to 40 mg of SC-SHA or 40 mg SC-SHA that had been preincubated for 1 hour with unlabeled S. sanguis FW213 cells. The cells and beads were incubated on an aliquot mixer at 37.degree. C. for 1 hour. The beads and adsorbed cells were allowed to settle, the supernatant was removed, and the beads were washed 3 times in the buffer. The amount of radioactivity associated with the beads and supernatant was determined in a Beckman LS7500 Liquid Scintillation Counter and the counts converted to number of cells bound to 40 mg SC-SHA (q) and number of free cells (c). S. mutans cells alone, curve (o) display the relationship characteristic of nonspecific binding. S. mutans attachment to preformed S. sanguis plaque, curve (.), s
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The invention described herein was made in the course of, or under, a grant from the National Institute for Dental Research.
This application is a continuation-in-part of application Ser. No. 467,800, filed Feb. 18, 1983, now abandoned.
This invention relates to a process for treating the oral cavity of mammals to block or reduce the attachment of microorganisms to surfaces of the teeth therein. The invention also relates to compositions useful for this purpose and to methods for their preparation.
Fives-Taylor Paula
Novotny Charles P.
Rose Shep K.
The University of Vermont and State Agricultural College
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