Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis

Definitions

• This invention relates to caries inhibiton.
• the invention also relates to gingivitis inhibition.
• the present invention provides an orally ingestible composition containing a caries and gingivitis inhibiting amount of a protein or a polypeptide or a salt thereof.
• the protein or polypeptide is a phosphoprotein or a polyphosphopeptide.
• the protein or polypeptide is an acidic phosphoprotein or polypeptide.
• the protein or polypeptide contains the amino acid sequence (X-Y-Z) where X and Z are a phosphoserine, phosphothreonine, phosphotyrosine, glutamate or asparate and Y is any amino acid.
• the protein or polypeptide contains a plurality of units each having the amino acid sequence (X-Y-Z) where X, Y and Z are as stated in above.
• the protein or polypeptide contains a group of formula (X-Y-Z)n where X, Y and Z are as stated in cl aim 4 and n is 1 or more.
• n is 3 or more.
• X and Z are phosphoserine.
• the protein or polypeptide is a polyphosphoserine.
• the phosphate groups of the polyphosphoserine are spaced at about 6.88 Angstrom Units.
• the protein is a casein.
• the protein is alpha-s-casein.
• the protein is phosvitin.
• the protein or polypeptide is in solution .
• the protein or polypeptide is one exhibiting a reduction in calcium dissolution rate of at least 45 nmol/min under the test conditions defined herein.
• the protein or polypeptide is one exhibiting a reduction in calcium dissolution rate of at least 80 nmol/min under the test conditions defined herein.
• the protein or polypeptide is one exhibiting a reduction in calcium dissolution rate of at least 90 nmol/min under the test conditions defined herein.
• the protein or polypeptide is one exhibiting a reduction in calcium dissolution rate of at least 95 nmol/rain under the test conditions defined herein.
• the protein or polypeptide is present as up to 10% by weight.
• the protein or polypeptide is present as up to 5% by weight.
• the protein or polypeptide is present as up to 2% by weight.
• the composition additionally contains urea.
• composition of this invention may be in the form of a foodstuff, confectionery, dentifrice, tablet or comprise a pharmacologically acceptable vehicle, solution of suspension far topical application to the teeth or a mouthwash.
• pharmacologically acceptable vehicle solution of suspension far topical application to the teeth or a mouthwash.
• Other modes of administering the protein or polypeptide would be acceptable if pharmacologically acceptable.
• compositions are chewing gum, breakfast foods, ice-cream and other frozen confectionery, confectionery, sweets and cakes as these are all known as caries problem foods.
• dentifrices, mouthwashes and preparations for topical application to teeth are dentifrices, mouthwashes and preparations for topical application to teeth
• ⁇ s - casein and other caseins are obtainable from milk
• phosvitin is obtainable from egg yolks
• suitable phosphoproteins include those which are obtainable from cereals, nuts and vegetables particularly in bran husks or sheaths.
• rice, wheat, oat, barley and rye brans are a source of such phosphoproteins.
• Polypeptides of interest include polyphosphoserine, p-olyglutamate and polyaspartate.
• the present invention also provides a process of inhibiting dental caries and/or tooth erosion and/or gingivitis comprising applying to the teeth with a carrier a cariostatic and/or antigingivitis agent selected from a protein or a polypeptide or a salt thereof.
• the present invention also provides a first test procedure for selecting among the proteins or polypeptides that may be used those that are most effective.
• TEST 1 The purpose of this test is to determine hydroxyapatite dissolution and in this respect since tooth enamel is largely composed of hydroxyapatite it is believed that useful comparisons can be made.
• Double distilled, deionised water (greater than 10 M ⁇ /cm) was used throughout.
• Analytical reagent grade chemicals were obtained from Ajax Chemicals, Australia. Hydroxyapatite-spheroidal was purchased from BDH, and phosvitin from Sigma Chemical Co., Missouri, U.S.A.
• the milk proteins were fractionated by the method of Zittle and Custer (1), and their purity assessed by polyacrylamide gel electrophoresis using a modification of the method of Groves and Kiddy (2).
• Inorganic phosphate was measured by the method of Itaya and Ui (3) and protein by the method of bradford (4). The determination of calcium was by atomic absorption spectrophotometry using 1% lanthanum chloride to prevent phosphate suppression. Results
• the proteins used for the study are listed in Table 1, they are all acidic proteins and included four phosphoproteins and three non-phosphorylated proteins from the whey fraction of bovine milk.
• the effect of the individual proteins on hydroxyapatite dissolution rate is shown in Table 2.
• Bovine serum 56,21 ⁇ - 4.7 - albumin a Residues per mol protein Table 2. Effect of phosphorylated and non-phosphorylated proteins on hydroxyapatite dissolution rate. Protein Reduction in Reduction in Amount of protein calcium phosphate bound dissolution dissolution rate a rate (nmol/min) (nmol/min) (mg)
• the effect of phosvitin on the dissolution rate of hydroxyapatite is shown in Figure 1.
• the protein caused an initial increase in the dissolution rate of phosphate which then decreased and approached a new steady state level; 63.8 nmol/min less than the rate prior to phosvitin application.
• the protein caused an immediate and marked drop in the calcium dissolution rate which then increased and approached a steadystate level 93.1 nmol/min less than that prior to phosvitin application.
• the amount of protein that passed through the column was measured and from this the amount retained was calculated 1.87 mg.
• the dissolution rate returned to the original value after phosvitin was eluted from the column with 10 ml of eluent buffer containing 1.5 M phosphate, followed by buffer not containing phosphate.
• Vitamin mixture a 1 a. Calcium and phosphate not detectable, fluoride content of complete diet was less than ⁇ .2 g per g dry weight, b. Vitamin and Salt mixture described in detail elsewhere.
• the animals were weighed daily and the amounts of powdered diet and liquid consumed over a 24 h period by each group was measured. After 42 days on the diet, the animals were killed by cervical dislocation and treated as described below. Caries evaluation.
• Fissure caries was assessed using the method of Konig, Marthaler and Muhlemann (1958) (5).
• the mandible was removed from each rat and placed in formol-saline.
• the jaws were the sectioned and stained by the method of Konig et al (1958)(5), as described by Green and Hartles (1966)(6) to provide series of 1 ⁇ ⁇ m thick longitudinal mesio-distal sections of the molar teeth. Only the main fissures of the first and second molar teeth were assessed for caries. Results Diet Consumption
• the animals drinking the 1% casein solution had 76.5% less carious fissures than the control animals (p ⁇ . ⁇ 1), and the animals consuming the 2% whey protein solution had 40.3% less carious fissures than the control group (p ⁇ . ⁇ 1).
• the correlation of caries incidence with the final weight of the rat was tested for the three group No correlation attained significance (p> ⁇ .1).
• Acidic proteins in the drinking water substantially reduced caries incidence of male Sprague-Dawley rats, however the phosphorylated protein (casein) caused a greater reduction than the non-phosphorylated whey proteins.
• S.mutans PK1 cells was studied by incubating the pretreated discs with 3 H-thymidine labelled cells (1 ⁇ 9 cells/ml) suspended in the imidazole buffer.
• the protein solutions used were all 5 mg/ml in imidazole buffer.
• the proteins and polypeptides studied were ⁇ s -casein, ⁇ -casein, ⁇ -casein, phosvitin, bovine serum albumin, histone III, histone VIII, ⁇ -lactalbumin, B-lactoglobulin, poly-l-lysine and poly-l-glutamate.
• the caseins were prepared by selective precipitation and the other proteins were purchased from Sigma Chemical Co., Missouri, U.S.A. Results
• Proteins Type Number of S.mutans cells adsorbed (x10 7 ) Control - 1.9 ⁇ .6 a ⁇ s1 -casein acidic phosphoprotein ⁇ .5 ⁇ .3 ⁇ - casein acidic phosphoprotein ⁇ .4 ⁇ .4 ⁇ - casein acidic phosphoprotein ⁇ .6 ⁇ .1 phosvitin acidic phosphoprotein ⁇ .5 ⁇ .1
• compositions in accordance with this invention as follows.
• the compositions contain from 0.5-20% by weight of protein or polypeptide.
• Example 1. Flour: In a device for mixing dry substances, 1% by weight of powdered sodium caseinate was blended with flour.
• Example 2 Cereal: A breakfast cereal was sprayed with a solution of calcium caseinate in water. The cereal flakes were then dried to produce a finished product containing 1% calcium caseinate.
• Example 3 Bread: 2% by weight of calcium caseinate was added to the flour during the mixing of ingredients for the manufacture of bread.
• Cake mix 1% by weight of calcium caseinate was added to the dry ingredients in the preparation of a cake mix.
• Confectionery In the preparation of confectionery 2 % by weight of calcium caseinate was added to the final mixture.
• Biscuit In the preparation of a biscuit mixture 5% by weight of calcium caseinate was added to the other dry ingredients during mixing.
• Example 7 Beverage: A beverage was prepared in which 1% Example 8. Tablet: A tablet was made containing 10% by weight of calcium caseinate together with excipients being flavouring matter and binding material.
• the requisite salt and salts of the selected protein or polypeptide are incorporated into dentifrice compositions in any suitable manner depending on whether a powder, paste or liquid preparation is to be produced.
• appropriate preparations of surface-active agents, binders, flavouring materials and other excipients required to achieve the required form of dentifrice are added.
• Tooth paste A toothpaste was prepared having the following composition:-
• Example 10 Toothpaste: A preparation as set out in example
• Example 11 Toothpaste A preparation as set out in example
• Toothpaste A preparation as set out in example was repeated but with the addition of ⁇ .1% mono sodium fluorophosphate in a suitable form.
• Tooth powder The following preparation was made:-
• Example 14 Dibasic calcium phosphate 94.1% " Example 14. Tooth powder: A preparation as set out in example 13 was made but with the addition of 1% mono sodium fluorophosphate in a suitable form.
• Example 15 Liquid dentifrice: A preparation was made consisting of:-
• Liquid dentifrice As for example 15 but with ⁇ .5% sodium fluoride added.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Birds (AREA)
• Epidemiology (AREA)
• Cosmetics (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Confectionery (AREA)
• Peptides Or Proteins (AREA)

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Cited By (27)

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Citations (12)

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• 1982
  • 1982-03-03 NZ NZ199891A patent/NZ199891A/en unknown
  • 1982-03-04 DE DE82900611T patent/DE3280378D1/de not_active Expired - Lifetime
  • 1982-03-04 WO PCT/AU1982/000022 patent/WO1982003008A1/en not_active Ceased
  • 1982-03-04 JP JP57500823A patent/JPS58500664A/ja active Granted
  • 1982-03-04 EP EP82900611A patent/EP0073210B1/en not_active Expired - Lifetime
• 1985
  • 1985-12-23 CA CA000498546A patent/CA1212627A/en not_active Expired

Patent Citations (12)

Non-Patent Citations (2)

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