CA1086653A - Oligomeric peptide having arginine unit to raise ph and reduce caries - Google Patents
Oligomeric peptide having arginine unit to raise ph and reduce cariesInfo
- Publication number
- CA1086653A CA1086653A CA280,752A CA280752A CA1086653A CA 1086653 A CA1086653 A CA 1086653A CA 280752 A CA280752 A CA 280752A CA 1086653 A CA1086653 A CA 1086653A
- Authority
- CA
- Canada
- Prior art keywords
- composition
- precursor
- arginine
- adjusting compound
- glycine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- 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
Abstract
ABSTRACT OF THE DISCLOSURE
Destruction of tooth tissues due to various microorganisms is slowed or prevented by the addition of arginine or arginine precursors to the mouth, especially oligomeric peptides having 2 to 4 amino acid units.
Destruction of tooth tissues due to various microorganisms is slowed or prevented by the addition of arginine or arginine precursors to the mouth, especially oligomeric peptides having 2 to 4 amino acid units.
Description
1~8G6S3 The present invention relates to a composition for reducing or preventing caries, and is based on two well accepted observations. Caries is more likely to occur when the pH of the mouth falls below a certain critical level depending on the resistance of the individual and on the duration for which the critical level is exceeded. The second observation is the recog-nition that saliva itself has a salutary effect on the aforementioned caries causing factors which includes some means for raising oral pH.
It has been clear for some time that when an abundance of carbo-hydrate, particularly sugar, is present in the mouth, conditions favoring the production of an acid pH in plaque are sure to be present. The plaque micro-flora form acid from exogenous or endogenous carbohydrate. The balancing of this acid production has been observed to be by means of producing alkaline substances which neutralize the cariogenic acids derived from the carbohydrates and return the pH of tooth surfaces to a level above that at which caries will occur.
The present invention relates to providing a means to enhance the natural defenses of the body against caries when the latter are the result of attack on the tooth by cariogenic acids. It further is directed to replacing or supplementing the natural protective function of saliva when it is dimin-ished by atrophy of the salivary glands or other impairments thereof which -;
diminish the secretion of saliva or the protective capability thereof.
According to the present invention, there is provided a compo-sition selected from the group consisting of a dental care product, a food product and a chew;ng gum, which composition comprises a source of a pH ad-justing compound or a precursor thereof having 2-4 amino acid units of which at least one unit is arginine, in an amount effective to combat caries by controlling the oral pH.
Thus, the invention seeks to diminish or eliminate caries in otherwise susceptible individuals by supplying suitable sources of pH adjust-ing compounds or precursors thereof. In one advantageous embodiment lQ866S3 the composition contains an oligomeric peptide having 2 - 4 amino acid units, one or more of which is arginine as the alkaline producing means.
It has been observed that plaque, the closely adhering, spongy organic material found on tooth surfaces accepts within its matrix molecules of certain size and shape. Oligomers of peptides are among those compounds which can penetrate plaque. It has been shown that these compounds pene-trate bacteria present in the mouth. It has been discovered that the material which most readily counteracts the acid produced when an abundance of carbohydrate, particularly sugar, is present is the amino acid arginine.
Surprisingly, it has been determined that an oligomeric peptide of 2 - 4 amino acid units, one or more of which is arginine, is even more effective in restoring mouth pH to a non-carious level.
It has been determined that generally, caries resulting from an acidic pH nearly ivariably occurs when a pH of about 5 or 5.1 occurs for a sufficient time while with only rare exceptions will caries occur if the pH is maintained at 6.1 or higher.
The question of duration of exposure of enamel to a pH lower than about pH 5 varies with individuals but certain generalities have been determined.
Two schemes of activity may be posited. In the first, the mouth is exposed to a limited amount of fermentable carbohydrate, usually sugar, after which the bacteria present in plaque convert the carbohydrate to acids, mainly acetic, lactic and propionic. In this case the pH drops as the above indicated acids are produced and a slow countering production of alkaline amines occurs as susceptible peptides or proteins give up amino acids which are decarboxylated by other oral bacteria. The two antagonistic reactions occur at rates such that the pH drop which is achieved between about 5 and 15 minutes will usually reach the pH level critical to the formation of caries unless the pH rise factor which has been found to be arginine and its precursors is present and is acted upon by oral bacteria so that the pH fall is reduced and the pH is returned to the normal by the end of about 45 minutes to 1 hour depending upon the particular mouthO
A second situation is represented by an availability of greater amounts of fermentable carbohydrate available for a longer time. The mouth pH in this case goes below pH 5 which is conducive to the formation of caries after about 15 minutes and remains there while the excess of fermentable carbohydrate is available. This can be for a period of 2 or more hours.
It is under these conditions that a more serious carious attack occurs but in the presence of the pH rise factor the duration is reduced.
Experiments were performed in vitro using supernatant saliva.
The saliva was obtained from random donors whose salivary secretions were paraffin block stimulated. The saliva donations may be pooled before or after sediment removal.
The naturally occurring effective oligomeric peptide in the saliva has the arrangement glycine-glycine-lysine-arginine with amino and car-. . .-~
boxyl termini. This compound was synthesized by conventional methods and has proved effective for the purposes of this invention and is the preferred pH rise factor. It being the compound which occurs naturally it is the ; first choice, but the possibility of an oligomeric pèptide having two or re arginine units might prove even more effective.
The arginine containing peptide rapidly enters plaque and also enters bacteria itselfO The oligomeric peptide is stored there protected from dilution providing a potential source of alkaline material to counter-act acid formation activated by the presence of dietary carbohydrate.
This storage capability suggests inclusion of the polypeptide pH rise factor in common dental products such as tooth pastes, tooth powders, mouth-washes and the like, as well as in chewing gums.
It has further been found that the oligomeric peptide pH rise factor is effective even when provided to the mouth simultaneously with carbohydrate substances which are operated upon by plaque bacteria to produce ~86653 acids. The addition of the pH rise factor to carbohydrate substances is an effective mear~s for supplementing the natural defenses of the body against caries.
The arginine containing oligomeric peptides are particularly suited as food additives in that many occur in nature, particularly the pre-ferred one of the present invention.
They are heat stable, tasteless, odorless and soluble in amounts beyond their effective level. They are aesthetically acceptable as used.
The pH differences in the mouths of caries prone and caries free subjects can be minimized by adding pH rise factor supplement to the former.
This is effective in pToportion to the amounts of oligomeric arginine peptide provided. A significant effect is produced with as little as 0.05 mM while as much as 3 mM and more continued to show improvement~
Particularly interesting cooperation beteeen the pH rise factor and fluoride ions may be had. Fluoride ion in minor amounts such as about 5ppm reduces tooth solubility generally. It further inhibits pH fall when the pH drops below about 5. The pH fall in the case of high sugar availabil-ity to 4.8 is held to 5.1 when 5 ppm of fluoride is present. This is about as high as fluoride ions alone can return the pH. When pH rise factor is also present, fluoride still inhibits the pH fall but the pH recovers earlier to safe levels of pH than when no factor is present.
The following examples are given by way of illustration and not by way of limitation.
EXAMPLES
Four sets of three 10 x 75 mm test tubes were provided with 0.2 ml of 8.4 mM of aqueous glucose solution. Set I was provided with 002 ml of pooled supernatant saliva. Set II was provided with 0.2 ml of 9.9 mM of the oligomeric peptide glycine-glycine-arginine. Set III was provided with 0.2 ml of 9.9 mM arginine and Set IV was provided with 002 ml of distilled water. Sequentially 0.2 ml of a 50:50 aqueous suspension of oral bacteria 1~866S3 was added to each test tube. me prepared test tubes were kept at 37C
in a water bath. pH readings were taken at 0 time when the bacteria were added and at 15, 30, 45, 60, 90, 120, 180 and 240 minutes thereafter. The pH values were as given in the following table.
TABLE
(minutes) Set I 7.4 6.25.9 6.1 6.3 6.4 6.5 6.6 6.6 Set II 7.4 6.86.6 604 6.6 606 6.7 7.2 7.6 Set III 7.3 5.85.4 5.2 4.9 5.0 5.0 5O3 5.8 Set IV 7.3 5.85.2 4.9 4.7 4.6 4.5 4.5 4.5 It is clear that supernatant saliva and an arginine supplement slows the pH fall in a carbohydrate environment. It is also evident that an arginine containing oligomeric peptide is more effective than arginine alone. In similar experiments, an arginine containing oligomeric peptide ;~ supplement acts to moderate the pH drop more than either saliva alone or or arginine alone and restores the pH to its initial level or better.
The identification of the pH rise factor suggests other areas wherein arginine containing oligomeric peptides could be utilized. These 20 compounds could be used in the regulation of many processes involving mic-roorganisms such as bacterial fermentations, wine making, antibiotic pro-duction, citric acid formation and others.
The invention has been described with respect to certain preferred embodiments but it will be understood that variations and modifications may be made therein without departing from the spirit of this invention and the scope of the appended claims.
. . .
It has been clear for some time that when an abundance of carbo-hydrate, particularly sugar, is present in the mouth, conditions favoring the production of an acid pH in plaque are sure to be present. The plaque micro-flora form acid from exogenous or endogenous carbohydrate. The balancing of this acid production has been observed to be by means of producing alkaline substances which neutralize the cariogenic acids derived from the carbohydrates and return the pH of tooth surfaces to a level above that at which caries will occur.
The present invention relates to providing a means to enhance the natural defenses of the body against caries when the latter are the result of attack on the tooth by cariogenic acids. It further is directed to replacing or supplementing the natural protective function of saliva when it is dimin-ished by atrophy of the salivary glands or other impairments thereof which -;
diminish the secretion of saliva or the protective capability thereof.
According to the present invention, there is provided a compo-sition selected from the group consisting of a dental care product, a food product and a chew;ng gum, which composition comprises a source of a pH ad-justing compound or a precursor thereof having 2-4 amino acid units of which at least one unit is arginine, in an amount effective to combat caries by controlling the oral pH.
Thus, the invention seeks to diminish or eliminate caries in otherwise susceptible individuals by supplying suitable sources of pH adjust-ing compounds or precursors thereof. In one advantageous embodiment lQ866S3 the composition contains an oligomeric peptide having 2 - 4 amino acid units, one or more of which is arginine as the alkaline producing means.
It has been observed that plaque, the closely adhering, spongy organic material found on tooth surfaces accepts within its matrix molecules of certain size and shape. Oligomers of peptides are among those compounds which can penetrate plaque. It has been shown that these compounds pene-trate bacteria present in the mouth. It has been discovered that the material which most readily counteracts the acid produced when an abundance of carbohydrate, particularly sugar, is present is the amino acid arginine.
Surprisingly, it has been determined that an oligomeric peptide of 2 - 4 amino acid units, one or more of which is arginine, is even more effective in restoring mouth pH to a non-carious level.
It has been determined that generally, caries resulting from an acidic pH nearly ivariably occurs when a pH of about 5 or 5.1 occurs for a sufficient time while with only rare exceptions will caries occur if the pH is maintained at 6.1 or higher.
The question of duration of exposure of enamel to a pH lower than about pH 5 varies with individuals but certain generalities have been determined.
Two schemes of activity may be posited. In the first, the mouth is exposed to a limited amount of fermentable carbohydrate, usually sugar, after which the bacteria present in plaque convert the carbohydrate to acids, mainly acetic, lactic and propionic. In this case the pH drops as the above indicated acids are produced and a slow countering production of alkaline amines occurs as susceptible peptides or proteins give up amino acids which are decarboxylated by other oral bacteria. The two antagonistic reactions occur at rates such that the pH drop which is achieved between about 5 and 15 minutes will usually reach the pH level critical to the formation of caries unless the pH rise factor which has been found to be arginine and its precursors is present and is acted upon by oral bacteria so that the pH fall is reduced and the pH is returned to the normal by the end of about 45 minutes to 1 hour depending upon the particular mouthO
A second situation is represented by an availability of greater amounts of fermentable carbohydrate available for a longer time. The mouth pH in this case goes below pH 5 which is conducive to the formation of caries after about 15 minutes and remains there while the excess of fermentable carbohydrate is available. This can be for a period of 2 or more hours.
It is under these conditions that a more serious carious attack occurs but in the presence of the pH rise factor the duration is reduced.
Experiments were performed in vitro using supernatant saliva.
The saliva was obtained from random donors whose salivary secretions were paraffin block stimulated. The saliva donations may be pooled before or after sediment removal.
The naturally occurring effective oligomeric peptide in the saliva has the arrangement glycine-glycine-lysine-arginine with amino and car-. . .-~
boxyl termini. This compound was synthesized by conventional methods and has proved effective for the purposes of this invention and is the preferred pH rise factor. It being the compound which occurs naturally it is the ; first choice, but the possibility of an oligomeric pèptide having two or re arginine units might prove even more effective.
The arginine containing peptide rapidly enters plaque and also enters bacteria itselfO The oligomeric peptide is stored there protected from dilution providing a potential source of alkaline material to counter-act acid formation activated by the presence of dietary carbohydrate.
This storage capability suggests inclusion of the polypeptide pH rise factor in common dental products such as tooth pastes, tooth powders, mouth-washes and the like, as well as in chewing gums.
It has further been found that the oligomeric peptide pH rise factor is effective even when provided to the mouth simultaneously with carbohydrate substances which are operated upon by plaque bacteria to produce ~86653 acids. The addition of the pH rise factor to carbohydrate substances is an effective mear~s for supplementing the natural defenses of the body against caries.
The arginine containing oligomeric peptides are particularly suited as food additives in that many occur in nature, particularly the pre-ferred one of the present invention.
They are heat stable, tasteless, odorless and soluble in amounts beyond their effective level. They are aesthetically acceptable as used.
The pH differences in the mouths of caries prone and caries free subjects can be minimized by adding pH rise factor supplement to the former.
This is effective in pToportion to the amounts of oligomeric arginine peptide provided. A significant effect is produced with as little as 0.05 mM while as much as 3 mM and more continued to show improvement~
Particularly interesting cooperation beteeen the pH rise factor and fluoride ions may be had. Fluoride ion in minor amounts such as about 5ppm reduces tooth solubility generally. It further inhibits pH fall when the pH drops below about 5. The pH fall in the case of high sugar availabil-ity to 4.8 is held to 5.1 when 5 ppm of fluoride is present. This is about as high as fluoride ions alone can return the pH. When pH rise factor is also present, fluoride still inhibits the pH fall but the pH recovers earlier to safe levels of pH than when no factor is present.
The following examples are given by way of illustration and not by way of limitation.
EXAMPLES
Four sets of three 10 x 75 mm test tubes were provided with 0.2 ml of 8.4 mM of aqueous glucose solution. Set I was provided with 002 ml of pooled supernatant saliva. Set II was provided with 0.2 ml of 9.9 mM of the oligomeric peptide glycine-glycine-arginine. Set III was provided with 0.2 ml of 9.9 mM arginine and Set IV was provided with 002 ml of distilled water. Sequentially 0.2 ml of a 50:50 aqueous suspension of oral bacteria 1~866S3 was added to each test tube. me prepared test tubes were kept at 37C
in a water bath. pH readings were taken at 0 time when the bacteria were added and at 15, 30, 45, 60, 90, 120, 180 and 240 minutes thereafter. The pH values were as given in the following table.
TABLE
(minutes) Set I 7.4 6.25.9 6.1 6.3 6.4 6.5 6.6 6.6 Set II 7.4 6.86.6 604 6.6 606 6.7 7.2 7.6 Set III 7.3 5.85.4 5.2 4.9 5.0 5.0 5O3 5.8 Set IV 7.3 5.85.2 4.9 4.7 4.6 4.5 4.5 4.5 It is clear that supernatant saliva and an arginine supplement slows the pH fall in a carbohydrate environment. It is also evident that an arginine containing oligomeric peptide is more effective than arginine alone. In similar experiments, an arginine containing oligomeric peptide ;~ supplement acts to moderate the pH drop more than either saliva alone or or arginine alone and restores the pH to its initial level or better.
The identification of the pH rise factor suggests other areas wherein arginine containing oligomeric peptides could be utilized. These 20 compounds could be used in the regulation of many processes involving mic-roorganisms such as bacterial fermentations, wine making, antibiotic pro-duction, citric acid formation and others.
The invention has been described with respect to certain preferred embodiments but it will be understood that variations and modifications may be made therein without departing from the spirit of this invention and the scope of the appended claims.
. . .
Claims (18)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A composition selected from the group consisting of a dental care product, a food product and a chewing gum, which composition comprises a source of a pH adjusting compound or a precursor thereof having 2-4 amino acid units of which at least one unit is arginine, in an amount effective to combat caries by controlling the oral pH.
2. The composition of claim 1 wherein said composition includes said pH adjusting compound or precursor in an amount sufficient to provide a concentration of from about 0.05 to about 3mM of said pH adjusting compound or precursor in the oral cavity.
3. The composition according to claim 1 wherein the major portion thereof is a dental care product.
4. The composition of claim 1 wherein the major portion thereof is a food product.
5. The composition of claim 1 wherein the major portion thereof is a chewing gum.
6. The composition of claim 3 which also contains an effective amount of fluoride ions.
7. The composition according to claim 1 wherein said pH adjusting compound or precursor thereof includes the amino acid units glycine-glycine-lysine-arginine or glycine-glycine-arginine.
8. The composition of claim 1 adapted to reverse within one hour the fall of oral pH induced by carbohydrates.
9. The composition of claim 1 wherein said composition includes said pH adjusting compound or precursor in an amount sufficient to provide a non-carious pH level in the oral cavity.
10. A method for making a composition which supplements the body's resistance to caries, comprising the step of adding a pH adjusting compound or precursor thereof to a carrier such as a food product base, dental care product base or chewing gum base; said pH adjusting compound or precursor thereof having 2-4 amino acid units of which at least one is arginine and wherein said pH adjusting compound or precursor thereof is added to said carrier in an amount effective to control the oral pH.
11. The method of claim 10 wherein the amount of said pH adjusting compound or precursor thereof is adapted such that said composition provides a concentration of from about .05 to about 3mM of said pH adjusting compound or precursor thereof in the oral cavity.
12. The method of claim 10 wherein said carrier is a dental care product.
13. The method of claim 10 wherein said carrier is a food product.
14. The method of claim 10 wherein said carrier is a chewing gum.
15. The method of claim 12 wherein said method further includes the step of adding to said carrier an effective amount of fluoride ions.
16. The method according to claim 10, 11 or 12, wherein said pH
adjusting compound or precursor thereof includes the amino acid units glycine-glycine-lysine-arginine, or glycine-glycine-arginine.
adjusting compound or precursor thereof includes the amino acid units glycine-glycine-lysine-arginine, or glycine-glycine-arginine.
17. The method of claim 11 wherein the amount of said pH adjusting compound or precursor thereof added to said carrier is adjusted such that said composition will reverse within one hour the fall of oral pH induced by carbohydrates.
18. The method of claim 11 wherein the amount of said pH adjusting compound or precursor thereof added to said carrier is adjusted such that said composition will provide a non-carious pH level in the mouth.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69753876A | 1976-06-18 | 1976-06-18 | |
| US697,538 | 1976-06-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1086653A true CA1086653A (en) | 1980-09-30 |
Family
ID=24801504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA280,752A Expired CA1086653A (en) | 1976-06-18 | 1977-06-17 | Oligomeric peptide having arginine unit to raise ph and reduce caries |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4154813A (en) |
| JP (1) | JPS5326331A (en) |
| AU (1) | AU515028B2 (en) |
| BE (1) | BE855658A (en) |
| CA (1) | CA1086653A (en) |
| DE (1) | DE2727150C2 (en) |
| DK (1) | DK270577A (en) |
| FR (1) | FR2362634A1 (en) |
| GB (1) | GB1579974A (en) |
| IE (1) | IE45390B1 (en) |
| IT (1) | IT1078339B (en) |
| LU (1) | LU77563A1 (en) |
| NL (1) | NL7706690A (en) |
| NZ (1) | NZ184396A (en) |
| ZA (1) | ZA773318B (en) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ199305A (en) * | 1980-12-31 | 1984-07-31 | Colgate Palmolive Co | Oral anticalculus composition |
| US4339431A (en) * | 1980-12-31 | 1982-07-13 | Colgate-Palmolive Company | Anticalculus oral composition |
| US4339430A (en) * | 1980-12-31 | 1982-07-13 | Colgate-Palmolive Company | Antibacterial oral composition |
| NZ199891A (en) * | 1981-03-04 | 1985-07-31 | Univ Melbourne | Caries-inhibiting compositions containing casein or x-s-casein or phosuitin |
| US4532124A (en) * | 1981-08-19 | 1985-07-30 | Development Finance Corporation Of New Zealand | Dental rinse |
| US4391798A (en) * | 1982-03-15 | 1983-07-05 | Colgate-Palmolive Company | Non-irritating dentifrice |
| JPS60156620A (en) * | 1983-12-22 | 1985-08-16 | ザ ユニヴアーシテイ オブ メルボルン | Dental caries controller |
| US4725576A (en) * | 1983-12-29 | 1988-02-16 | Research Foundation Of State University Of New York | Fungicidal polypeptide compositions containing L-histidine and methods for use therefore |
| DE3417393C2 (en) * | 1984-05-10 | 1986-10-30 | Adolf Prof. Dr. 3220 Alfeld Knappwost | Means for increasing the pH of dental plaque and processes for their manufacture |
| JPH074576B2 (en) * | 1984-07-30 | 1995-01-25 | 富士車輌株式会社 | Wind power sorter |
| JPH0233905Y2 (en) * | 1985-08-02 | 1990-09-11 | ||
| US5258067A (en) * | 1988-06-25 | 1993-11-02 | Bayer Aktiengesellschaft | Liquid for conditioning tooth or bone substance |
| JPH0768111B2 (en) * | 1990-03-09 | 1995-07-26 | サンスター株式会社 | Oral composition |
| US5891459A (en) * | 1993-06-11 | 1999-04-06 | The Board Of Trustees Of The Leland Stanford Junior University | Enhancement of vascular function by modulation of endogenous nitric oxide production or activity |
| US5945452A (en) * | 1993-06-11 | 1999-08-31 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of vascular degenerative diseases by modulation of endogenous nitric oxide production or activity |
| JP3566374B2 (en) * | 1994-02-03 | 2004-09-15 | 花王株式会社 | Oral composition |
| US5762911A (en) * | 1996-03-05 | 1998-06-09 | The Research Foundation Of State University Of New York | Anti-caries oral compositions |
| US6805883B2 (en) | 1998-03-12 | 2004-10-19 | Mars, Incorporated | Food products containing polyphenol(s) and L-arginine to stimulate nitric oxide |
| US7371415B1 (en) | 1998-04-03 | 2008-05-13 | The Daily Wellness Company | Method and composition for improving sexual fitness |
| US20050196470A9 (en) * | 1998-04-03 | 2005-09-08 | Wuh Hank C | Method and composition for enhancing sexual desire |
| AU3221599A (en) * | 1998-04-03 | 1999-10-25 | Daily Wellness Company, The | Compositions comprising l-arginine, ginseng and gingko biloba for enhancing blood circulation |
| IL141250A0 (en) * | 1999-06-05 | 2002-03-10 | Univ Leland Stanford Junior | Method and composition for inhibiting cardiovascular cell proliferation |
| US6436370B1 (en) * | 1999-06-23 | 2002-08-20 | The Research Foundation Of State University Of New York | Dental anti-hypersensitivity composition and method |
| US6497885B2 (en) | 2000-12-22 | 2002-12-24 | The Daily Wellness Company | Method and composition for improving fertility health in female and male animals and humans |
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| US20050192210A1 (en) * | 2004-03-01 | 2005-09-01 | Rothbard Jonathan B. | Compositions and methods for treating diseases |
| MX2008013618A (en) | 2006-05-09 | 2008-10-30 | Colgate Palmolive Co | Oral care regimen. |
| US20080274065A1 (en) * | 2006-05-09 | 2008-11-06 | Richard Scott Robinson | Oral Care Regimen |
| JP4709735B2 (en) * | 2006-12-04 | 2011-06-22 | 花王株式会社 | Coaggregation inhibitor of oral bacteria |
| AR070695A1 (en) * | 2008-02-08 | 2010-04-28 | Colgate Palmolive Co | COMPOSITIONS AND DEVICES FOR DENTAL USE. APPLICATIONS. METHODS |
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| TWI451878B (en) * | 2008-02-08 | 2014-09-11 | Colgate Palmolive Co | Use of l-arginine, in free or salt form,and a fluoride,for the manufacture of a dentifrice composition and dentifrice composition |
| AU2009212335B2 (en) * | 2008-02-08 | 2011-12-01 | Colgate-Palmolive Company | Compositions comprising basic amino acid and soluble carbonate salt |
| CN102215811A (en) * | 2008-02-08 | 2011-10-12 | 高露洁-棕榄公司 | Effervescent compositions |
| US9029598B2 (en) | 2009-12-18 | 2015-05-12 | Colgate-Palmolive Company | Methods for production of arginine biocarbonate at low pressure |
| AU2010332017B2 (en) | 2009-12-18 | 2013-08-15 | Colgate-Palmolive Company | Method for production of high concentration of arginine bicarbonate solution at high pressure |
| JP5723001B2 (en) | 2010-06-23 | 2015-05-27 | コルゲート・パーモリブ・カンパニーＣｏｌｇａｔｅ−Ｐａｌｍｏｌｉｖｅ Ｃｏｍｐａｎｙ | Oral composition for treatment |
| MX366533B (en) | 2012-12-06 | 2019-07-12 | Colgate Palmolive Co | Oral gel for sensitivity and tooth pain. |
| CN107353351B (en) * | 2017-08-30 | 2020-06-23 | 四川大学 | Double-effect caries-preventing polypeptide, polypeptide derivative, polypeptide medicinal salt and application |
| CA3155474A1 (en) | 2019-09-30 | 2021-04-08 | The Procter & Gamble Company | Oral care compositions comprising hops beta acid and fluoride |
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| WO2021062607A1 (en) | 2019-09-30 | 2021-04-08 | The Procter & Gamble Company | Oral care compositions comprising hops beta acid and amino acid |
| CA3191784A1 (en) | 2020-09-28 | 2022-03-31 | The Procter & Gamble Company | Oral care compositions comprising prenylated flavonoids |
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| WO2022067141A1 (en) | 2020-09-28 | 2022-03-31 | The Procter & Gamble Company | Aqueous compositions comprising hops-metal complex |
| BR112023002550A2 (en) | 2020-09-28 | 2023-04-04 | Procter & Gamble | COMPOSITION FOR ORAL TREATMENT INCLUDING HOPS AND FLAVORS |
| EP4312956A1 (en) | 2021-03-25 | 2024-02-07 | The Procter & Gamble Company | Oral care compositions comprising hops and sweetener |
| CN117083053A (en) | 2021-03-25 | 2023-11-17 | 宝洁公司 | Edible oral composition comprising hops |
| CA3214487A1 (en) | 2021-03-25 | 2022-09-29 | The Procter & Gamble Company | Oral care compositions comprising hops |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL278724A (en) * | ||||
| GB1352420A (en) * | 1971-06-18 | 1974-05-08 | Ajinomoto Kk | Arginine derivatives their production and their use |
| US3932608A (en) * | 1971-08-30 | 1976-01-13 | General Mills, Inc. | Food composition |
-
1977
- 1977-06-02 ZA ZA00773318A patent/ZA773318B/en unknown
- 1977-06-08 AU AU25933/77A patent/AU515028B2/en not_active Expired
- 1977-06-14 BE BE178418A patent/BE855658A/en not_active IP Right Cessation
- 1977-06-15 NZ NZ184396A patent/NZ184396A/en unknown
- 1977-06-16 DE DE2727150A patent/DE2727150C2/en not_active Expired
- 1977-06-17 CA CA280,752A patent/CA1086653A/en not_active Expired
- 1977-06-17 NL NL7706690A patent/NL7706690A/en not_active Application Discontinuation
- 1977-06-17 GB GB25507/77A patent/GB1579974A/en not_active Expired
- 1977-06-17 LU LU77563A patent/LU77563A1/xx unknown
- 1977-06-17 FR FR7718708A patent/FR2362634A1/en active Granted
- 1977-06-17 JP JP7117877A patent/JPS5326331A/en active Granted
- 1977-06-17 DK DK270577A patent/DK270577A/en not_active Application Discontinuation
- 1977-06-17 IE IE1246/77A patent/IE45390B1/en unknown
- 1977-06-17 IT IT24820/77A patent/IT1078339B/en active
-
1978
- 1978-01-12 US US05/868,933 patent/US4154813A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| IT1078339B (en) | 1985-05-08 |
| FR2362634A1 (en) | 1978-03-24 |
| FR2362634B1 (en) | 1980-05-09 |
| US4154813A (en) | 1979-05-15 |
| DE2727150C2 (en) | 1986-08-21 |
| JPS5326331A (en) | 1978-03-11 |
| NZ184396A (en) | 1978-07-28 |
| JPS6259093B2 (en) | 1987-12-09 |
| ZA773318B (en) | 1978-04-26 |
| IE45390L (en) | 1977-12-18 |
| IE45390B1 (en) | 1982-08-11 |
| LU77563A1 (en) | 1977-09-19 |
| DK270577A (en) | 1977-12-19 |
| BE855658A (en) | 1977-12-14 |
| AU515028B2 (en) | 1981-03-12 |
| GB1579974A (en) | 1980-11-26 |
| DE2727150A1 (en) | 1977-12-29 |
| AU2593377A (en) | 1978-12-14 |
| NL7706690A (en) | 1977-12-20 |
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