JPH07505400A - dental preparations - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] dental preparations field of invention The present invention inhibits tooth enamel demineralization. related to things.

More specifically, it has a negative impact on remineralization. water-soluble phosphates, especially birophosphate or triphosphate, to inhibit demineralization without Concerning the use of lipolyphosphate. This prevents or reduces caries provide the means for

Much research has been done to reduce caries by chemical means. There are many caries There are many causes. The most commonly considered is enamel demineralization. Demineralization most widely used to prevent and remineralize enamel Research has shown that fluoride ions are introduced into the oral cavity via topical or other means of short-term topical application. It is to make it exist. Fluoridated drinking water has a material impact that reduces dental caries. did. Other research has shown that dentifrices, pastes applied directly to the teeth by professionals, Oral mouth rinses containing fluoride ions are used as a means of dental fluoridation.

Toothpastes, pastes and laxatives often contain alkali metal fluorides, monofluors, etc. Low levels of fluoride salts as alkali metal salts of orophosphoric acid and stannous fluoride Contains. A typical and effective fluoride concentration for these types of products is 110 It is on the order of 0 ppm. To date, inhibiting enamel demineralization and resulting in , no other chemical studies were developed as a means to prevent or treat dental caries.

Certain types of water exemplified by the alkali metal birophosphates and tripolyphosphates Soluble phosphates inhibit enamel demineralization, and they appear in superficial caries-like lesions. It was found that fluoride ions do not interfere with the remineralization phenomenon. This discovery This makes it possible to provide anti-caries dental preparations that do not use chemical compounds.

Summary of the invention The invention has two aspects. One, in an orally acceptable carrier, substantially is a demineralization inhibitor consisting of a non-toxic effective amount of water-soluble pyrophosphate or tripolyphosphate. Inhibiting enamel demineralization, which is characterized by treating teeth with a preparation containing an agent. A method for reducing or preventing dental caries in humans.

In a second aspect, the invention provides an orally acceptable carrier and a substantially non-toxic Enamel demineralization consisting of an effective amount of water-soluble pyrophosphate or tripolyphosphate. by reducing or preventing demineralization characterized by comprising an inhibitor; orally acceptable dental caries prevention formulations in humans.

Detailed example In its broadest embodiment, the invention inhibits tooth enamel demineralization and its consequences. As a result, certain restorations are being used as a means to reduce or prevent dental caries. Use phosphate salts. Orally acceptable rather than existing in acid or salt form The presence of water-soluble phosphate was found to be the decisive factor. Such phosphates are , orthophosphate, birophosphate, polyphosphate (stable phosphate) or metallic phosphate (cyclic phosphate). Preferred phosphates are birophosphate and triphosphate. It is a polyphosphate. As far as the ionic forms of phosphates are concerned, these phosphorus The respective acid forms of the acid salts should not be used. That is, H, P, O,. or H, P.

Acidic phosphates such as 07 should not be used. Partially neutralized form used however, the fully neutralized form is usually preferred. Ia for periods 2.3 and 4 Salts of group alkali metals are preferred, especially the sodium and potassium forms and Mixtures thereof are preferred. Most preferably Na5PsO+. Alone or Na4P 20t and a mixture of P2O7. Although this is preferable, Several types of phosphate salts and ionic forms may be included in one preparation. stomach. The phosphate salt may be anhydrous or hydrated.

Many commercial sources sell suitable phosphate preparations. In particular, pyrroline Potassium acid and potassium pyrophosphate and sodium tripolyphosphate are It is available from many companies. Alternatively, this salt may be purchased by commercial sources. Standards should be established by those performing drug formulation services using publicly available techniques and methods. It is a customary product prepared for the purpose of In these dental preparations, topical Pure phosphate preparations that meet regulatory requirements should be used.

The effective concentration of phosphorus M salt depends on the type of phosphate selected, its water solubility, and the product. depending on the type of toothpaste (i.e., toothpaste, toothpaste, chewing gum); influenced by the nature and chemical or physical properties of the carrier and co-formulation excipients. It will be done. Some ingredients or formulations have higher available phosphate content .

In any case, an effective amount is phosphoric acid without other demineralization inhibitors or remineralization agents. Enamel treatment to the extent that it reduces caries by a statistically significant means relative to the no-salt control. This is the amount that reduces mineral demineralization.

As a practical matter, while not intending to be bound by such a low limitation, approximately 2 % or more by weight of phosphate ions may be used in orally acceptable preparations. When used in the usual conventional form, it provides an effective anti-caries preparation. Ru. The preferred baseline for toothpastes, gels and liquids is 5 wt. %. Regarding sodium tripolyphosphate concentration, 5% W/W is the preferred amount. It is. For birophosphate, the preferred amount is about 1 tetrasodium birophosphate. 8% and tetrapotassium pyrophosphate 4.0%. These amounts are for pastes and When combined with excipients commonly used to formulate gels and Sufficient availability to inhibit enamel demineralization to the point that erosion is usefully reduced. phosphate should be provided. Phosphate levels of barrienoyone and semen Density may also be used when it is necessary to maximize the effectiveness of the phosphate in a given formulation. can be done when appropriate. Phosphates are available in dental tablets, lozenges and High percentage of total ingredient profile in dry formulations like chewing gum Represents a percentage.

These phosphates may be present in any orally acceptable carrier. can. The only limitation is the phosphate force available to interact with the tooth enamel The formulation must be suitable for use within approved guidelines. should not have any harmful or undesirable effects on the teeth or oral cavity. That is.

Many orally acceptable formulations are known in the dental arts. speak widely Examples of these include toothpastes (pastes, gels and liquids); powders, mouth rinses, dental tablets, dental lozenges, and dental chewing gums Examples include: Three of the most preferred formulations are toothpaste, gel and a fungal drug. These are orally acceptable for use in the present invention. The following is a detailed explanation of the formulation.

Toothpastes, gels and liquid formulations contain certain abrasives containing certain water-soluble phosphates. Prepared using conventional ingredients, taking care that they are incompatible with salts. These valid Certain limitations are detailed below. Apart from this one limitation, quite a lot of dental Permissible abrasives, wetting agents, cleaning agents, sweeteners, flavors, antibacterial agents, and colorants Combinations such as pigments and pigments can be used. Preferred toothpaste or toothpaste The agent contains about 5% birophosphate or tripolyphosphate, about 10-80% wetting agent, Approximately 0.25-5% detergents, up to 2% sweeteners and flavoring agents (combined) , colorants, binders and thickeners, and stable flowable pastes or gels. Contains sufficient water to prepare

Abrasives contemplated for use in the present invention are suitable for use without over-polishing the dentin. It may be a substance. Examples of these include silica, including gels and precipitates; Calcium birophosphate, calcium/umum polymetaphosphate, insoluble sodium polymetaphosphate aluminum, alumina hydrate, and individual concentrated products of urea and formaldehyde and the resinous abrasives disclosed in tJ, s, Patent No. 3.070.510. (which is hereby incorporated by reference). polishing Mixtures of agents may also be used. Certain abrasives are not compatible with the phosphates.

For example, calcium carbonate, dicalcium orthophosphate dihydrate, and phosphoric acid Tricalcium is best avoided if you want to achieve the maximum effectiveness of water-soluble phosphates. It is.

Various types of silica dental abrasives may over-abrasive tooth enamel or dentin. Able to provide exceptional dental cleaning and polishing unique effects without polishing.

Silica abrasives are exceptionally compatible with many ionic substances, including phosphates, which is the subject of this invention. It is also possible to adapt to For this reason, they are preferred for use herein. stomach.

Silica abrasives as well as other abrasives useful herein generally have a It has an average particle size in the range of ~30 microns, preferably 5-15 microns.

Silica abrasives are available from U,S Patent No. 3,538.230 and U,S Patent No. 3. , 862.207, precipitated silica such as silica, xerogel, etc. may be silica gel (incorporated herein by reference). preferred W, R, Grac e & Company) Davison Chemical Division (Davis on Chemical Division) l: Therefore, 'nroid J (S yloid, a silica xerogel sold under the trademark yloid (trade name). preferable Precipitated silica materials include JM Tuber Corporation (J, Zeopunto J (Zeopunto J) by M. odent, trademark name). These silica Abrasives are disclosed in U.S. Patent No. 4.340.583 (attribution cited (incorporated into this specification).

Abrasives in the dentifrice compositions described herein are If present, it is present at a level of about 6% to about 70%, preferably about 15% to about 25%.

If the composition is a toothpaste, 90% is the highest level used.

Flavoring agents can be added to the dentifrices and other compositions of the invention.

Suitable flavoring agents include oil of wintergreen, oil of peppermint, Includes mint oil, satsafras oil, and clove oil. Sweeteners are also useful. ri, aspartame, acesulfame, saccharin, dextrose, rebro and/or sodium clamate. Flavoring agents and sweetening agents , generally used at a level of about 1005% to about 2% by weight in the compositions of the invention. It will be done.

The dentifrice composition of the present invention may contain an emulsifier. Suitable emulsifiers are moderately It is stable and foams over a wide pH range; Synthetic organic detergents include ion type, nonionic type, cationic type, zwitterionic type and amphoteric type organic synthetic detergents. can be lost. Nonionic surfactants are preferred. Many of these suitable surfactants is disclosed in U.S. Patent No. 4.051.234 (the present invention is hereby incorporated by reference). shall be part of the specification).

Water is also present in the toothpaste compositions of the present invention. For the preparation of commercially suitable compositions The water used in the process is preferably deionized and free of organic impurities. stomach. Water is generally about 10% to 70% by weight of the toothpaste, preferably about 2% by weight of the toothpaste. It consists of 0% to 40% by weight. These amounts of water include the free water added, and sorbitol or other polypropylene produced as a diluent when water is the diluent. Includes free water introduced with other substances such as in the case of alcohols.

Thickeners are commonly added to toothpastes and gels to achieve the desired consistency - provide. Preferred thickeners include carboxyvinyl polymers, carrageenan, Droxyethyl cellulose and carboxin methylcellulose sodium and cellulose such as carboxin methyl hydroxyethyl cellulose sodium - It is a water-soluble salt of sether. Karaya gum, gum arabic and tragacanth Using natural gums such as gum and polysaccharide gums such as xanthan gum. It can also be used. Colloidal magnesium aluminum silicate or finely divided Silica can be used as part of a thickening agent to further improve texture. Ru. Hydroxyethylcellulose is a preferred binder. 0°5 of the total composition Thickeners may be used in amounts of % to 5.0% by weight.

To protect the toothpaste from hardening, it is desirable to include a humectant in the toothpaste. Delicious. Suitable wetting agents include glycerin, at a level of about 10% to about 70%; Included are sorbitol and other edible polyhydric alcohols such as PEG.

Antibacterial agents can be added to these pastes and gels (as well as rutting agents). good. Any one of a number of antimicrobials or agents may be used. Triclosan , that is, 5-chloro-2-(2,4-dichlorophenoxy)phenol is -This is an example. A useful group of antibacterial agents are cationic antibacterial agents. in toothpaste Cationic antimicrobial agents suitable for use include: (i) quaternary class ammonium compounds, for example, one or two substituents on the quaternary nitrogen 0, preferably 10 to 18 carbon atoms, preferably an alkyl group optionally containing amines, esters, oxygen, sulfur, or heterocycles. A good quaternary ammonium compound. The remaining nitrogen substituents contain a small number of carbon atoms, e.g. preferably 1 to 7, preferably alkyl, such as methyl or ether. Chill or benzyl. Anion is an orally acceptable salt-forming group . Examples of such compounds include benzalkonium chloride, dodecyltrimethyl Ammonium chloride, benzyldimethylstearylammonium chloride, Tilttrimethylammonium bromide, benzoethonium chloride (diisobutyl rufenoquinoethquinethyldimethylbenzylammonium chloride), and Examples include methylbenzoethonium chloride: (U) hexadenorviridine Um chloride, cetylpyridinium chloride, and alkylisoquinolinium Pyridinium and isoquinolinium compounds exemplified by bromide: (tit)hexetidine (5-amino-1,3-bi(2-ethylhexyl)-5 -pyrimidine derivatives such as (methylhexahydropyrimidine); (tv)isothi Hexamidine ionate (4,4'-diamondin-a, W-diphenoquinohexa Aniline derivatives such as (V) octenidine (N, N'[ 1,10-decanediyldi-1(4H)-pyridinyl-4-yridine]bis(1 -octaneamine) dihydrochloride), and bispyridine derivatives such as (vi) Biguanides such as: (a) p-chlorobenzyl biguanide and N'-(4-chlorobenzyl)-N ”-(2,4-dichlorobenzyl)biguanide, such as mono-biguanide, (b ) General formula (1): %formula% [In the formula, A1 and A are independently optionally (CI-4)alkyl, (CI-4) Alcoquine, nitro, halogen, (CI-+z)alkyl group or (C4-+i ) phenyl optionally substituted by a ring group: X, and X are independently is (CI-s)alkylene; R and R1 are independently hydrogen, (CI-+t)alkyl, or aryl(CI-g)alkyl: Zl and Z are independently 0 or 1.

Q is CH2, oxygen, sulfur or aryl; n of each (CHx)t+ group is independently an integer from 1 to 12, but the sum of both n's does not exceed 12.

Aryl is phenyl, naphthyl or other aromatic ring] Biguanidide and its orally acceptable acid addition salts.

Preferred compounds are chlorohequindin and alequindin.

(C) Poly(biguanides) such as polyhexamethylene biguanide hydrochloride.

Effective amounts of antimicrobial agents range from about 0.005 to 10% weight/weight (W/W), preferably preferably 0005 to 5%, more preferably 005 to 2.5%, and most preferably More specifically, it is 1.0% w/w.

Optional ingredients useful in any of the compositions of the invention that include a cationic antimicrobial agent include: It is an antistain agent. Cationic antibacterial agents are When used at fairly high levels, it can cause staining. As a coloring preventive agent, U, S, as disclosed in Patent No. 4.256.731 (the present invention is hereby incorporated by reference) Examples include carboxylic acids such as Other drugs include U, Aminocarboxyla as disclosed in Patent No. 3.937°807 Code compounds; U, S, Zika as disclosed in Patent No. 4.080.441; Rubonic acid ester: and U.

Phosphonoacetic acid as disclosed in S Patent No. 4.118.474 may be mentioned. Ru. All of these patents are incorporated herein by reference.

Make it flexible when mixing pastes and for consumer use. or for filling into solid tube-type containers or other conventional container forms; Conventional manufacturing techniques can be used. Toothpaste prepared according to the invention or gel formulations, there are no container limitations, to the best of our knowledge. .

The toothpaste of the present invention is a uniformly colored or striped toothpaste. It is prepared in the form of For filling toothpaste tubes with striped toothpaste A suitable device is disclosed in UK8 patent application no. 962,757.

Conventional mouthwashes can be prepared using the phosphate salts of the present invention. Containing drugs are generally about 20.1 to about 2:1 water/ethyl alcohol solution, and preferably It consists of other ingredients such as bars, sweeteners, humectants and surfactants. A suitable frame Rebar agents include wintergreen oil, peppermint oil, and spearmint oil. , satsafras oil, and butterfly oil. sweetness that can be used Agents include aspartame, acesulfame, These include cullin, dextrose, lebulose and sodium shiframate. It will be done. Suitable wetting agents include sorbitol and glycerin, while , suitable surfactants include oleate ester of sorbitol and lauri acid ester, its anhydrous condensate with ethylene oxide, and its anhydrous condensate with ethylene oxide. Examples include condensates with propylene oxide.

Other types of surfactants used are amphoteric surfactants. Hermaphrodites useful in the present invention Sudsing agents are those in which the aliphatic group is linear or branched. chain, one of the aliphatic substituents containing about 8 to about 18 carbon atoms and the other aliphatic substituent containing about 8 to about 18 carbon atoms. Anionic water-soluble groups, e.g. carboxinate, sulfonate, sulfate , aliphatic secondary and tertiary amines containing phosphates or phosphonates A wide range of derivatives can be described.

Generally, on a weight basis, the present powder contains 0.5% to 5% phosphate, ethyl Alcohol 5% to 30% (preferably 5% to 20%), wetting agent 0% to 25% ( Preferably 3% to 20%), surfactant 0% to 25% (preferably 0.01%) %-2.0%), sweetener O%-5% (preferably 0.005%-03%), Leber agent 0% to 03% (preferably 0.03% to 0.3%), preservative 11 %, optionally from pHW moderator and balance water Become.

The pH of the stimulant and/or its pH in the mouth is Any pH that is safe may be used. Generally, the pH is from about 3 to about 10, preferably Preferably, it is adjusted to about 4 to about 8.

Conventional manufacturing techniques and packaging materials can be used for these impregnators. Ru.

Other excipients include lozenges and chewing gum. Such a group Ingredients useful in the compositions include those disclosed in U.S. Patent No. 4,083,955. (which is incorporated herein by reference).

Products using these phosphates should be used in a conventional manner. example For example, if you brush your teeth with a toothpaste containing such water-soluble phosphates, thus making phosphate available to the tooth and thus inhibiting caries formation. or reduce the occurrence of caries in humans who are susceptible to caries formation. Ru. Containers are used for the prevention of dental caries in susceptible humans or for the prevention of dental caries in susceptible humans. For the prevention of further caries development in strong humans, in the normal and accepted form is also used. Dental powders as well as tablets, lozenges and dental tubes - Ingham is usually used if the effect is to be realized to its fullest extent. regularly used in the form of

The invention is illustrated by preferred embodiments in the following examples. all parts and percentages are by weight based on the total weight of the product unless otherwise specified. these fruits The examples are presented to illustrate the invention, and in no case limit its scope. It is not determined. Below, to determine what is held by the inventor: Referenced in the claims.

A toothpaste can be prepared using the following ingredients and two types of phosphates: Wear.

Table 1 - Tube formulation Ingredients %W/W (lipolyphosphate) %V/V (birophosphate) PEG-8, FCC (PEG 400) 3.00 3.00 Xanthan rubber 0.700 0.6000 Sorbitol USP (70%) 29.9322 28.476 1 Norica hydrate (Zeofree 113) 14.000 i4. oo.

Sodium tripolyphosphate 5.000 Sodium birophosphate 1.810 Potassium pyrophosphate 4.000 Sodium hydroxide (50% aqueous solution) 0.900 Glycerin 10.000 1 0.000 flavor o, soo o, so.

Sodium lauryl sulfate 1.150 1.150 Sodium saccharin 0. 214 0.214 D&C Yellow #10 (0.2%) 0.2015 0.2 015 Titanium dioxide 0.7235 0.7235 Sodium benzoate 0.1 00 0.100 In these two formulations, PEG-8 is It's a call.

It, along with sorbitol and glycerin, is a humectant. xantanga Zeofree 153 is a binder and thickener. The three types of pigments are WithKline Beecham Consumer Blang Product name of Beecham ConsuIIer Brands: Aqua Freneyu Tri-col products such as those sold under Aquafresh In this formulation as should be present as ored product) Can be mentioned.

Due to the presence of birophosphate and tripolyphosphate, the transparent gel-like formulation.

cannot be prepared. By removing three dyes from the formulation, A gel toothpaste can be prepared, although it is an opaque gel.

Pump dispensers are a favorite of many toothpaste users. below The formulation can be used with a pump dispenser system.

Table 2 - Pump dispenser formulations Ingredients %v/w ()Iff lilinoate) %W/W (birophosphate) PEG-8 , FCC (PEG 400) 3.00 3.00 Xanthan gum 0.700 0.6000 Sorbitol USP (70%) 29.609 28.253 Norica hydrate (Zeofree 153) 8. OOO7, OOO silica hydrate (ze Offly 113) 14.000 14.000 Sodium tripolyphosphate 5 ．． 000 Sodium birophosphate 1.810 Potassium pyrophosphate 4.000 Sodium hydroxide (50% solution) 0.900 Glycerin 10.000 10 ．． 000 flavors o, soo o, so.

Sodium lauryl sulfate 1.150 1.150 Sodium saccharin 0. 214 0.214 FD & C Blue #1 (0.2%) 0.2478 0.24 78D&C Yellow #10 (0.2%) 0.2015 0.2015 Chi dioxide Tan 0.9560 0.9560 Sodium benzoate 0.100 0.20 0 Example 2 The anti-caries-containing drug using birophosphate of the present invention is illustrated by the following formulation: Ru.

Ethyl alcohol, 190 proof 8.00 glycerin, 99% L], S, P , 8.000 Sodium birophosphate 2.060 Potassium pyrophosphate 0.710 Flavor 0.200 Menthol 0.007 Cremophor RH-600,200 Pluronic (P luronic) F-108 (surfactant) 0.100 Pluronic F-1 27 (Surfactant) 0.100 Benzoin #i 0.100 Satucharin sodium 0.060 FD&C31 (0.2% solution) 0.140FD&C Yellow #5 (0.2% solution) Liquid) 25% phosphoric acid solution to adjust pH to 0.900 Add phosphoric acid as necessary Mix these ingredients together, except for a small amount of water and adjust the pH to the desired value. The solution is then made up to volume with water. This penetrant is a conventional beer or packed in containers.

A similar antifungal drug is prepared according to the following formulation, except for the use of tripolyphosphate.

sandbags Ethyl alcohol, 190 proof 8.00 glycerin, 99% U, S, P, 8.000 Sodium tripolyphosphate 0.50 Talemophor RH-600,200 Pluronic F-108 (surfactant) 0.100 Pluronic F-127 ( Surfactant) 0.100am 9, aromatic acid o, io.

Sodium saccharin 0.060 FD&C #1 (0,2% solution) 0.140FD&C Yellow #5 (0,2% Solution) 25% phosphoric acid solution to adjust pH to 0.900 Deionized if necessary Add appropriate amount of on water to 100°00% Example 3 How to test phosphate efficacy The potency of these phosphates was determined using the following protocol: Simple Color A minute prepared dentifrice (toothpaste) in a tube. All have the same base This includes tripolyphosphate, birophosphate or one of these phosphates. was added together with NaF. The control was a dentifrice base. The table below shows the Indicates the active concentration in the agent.

Product Description (Fluoride as NaF, 1100 ppm F-free if indicated) Sodium tripolyphosphate (5%) F-free sodium birophosphate/potassium um (1,8/4゜0%) toothpaste base Sodium tripolyphosphate containing F- The identity of the sodium/potassium pyrophosphate product containing F- Technicians were not informed until the data had been evaluated and data collected. all fruit The experiment was carried out using color-coded tubes and a similar color-coded tube to keep the operator hidden. The experiment was carried out using a full laboratory shelf and test tubes.

The only partial destruction of miscoloring is the addition of corrections in hot J experiments. when it becomes necessary to describe an operator that is a radio tracer. It was.

In vitro testing of fluoride-containing products and fluoride products containing anti-tartar agents A pH cycling (demineralization/remineralization) model for research is Featherstone ( F. etherstone) et al., Caries Res., 1988; 22: 337-341. This model is pre-installed around orthodontic brackets. was found to mimic the results found by the inventors in vivo in [Oreilly (0' Re1ly) and Featherstone (F e atherstone), Ars, J., Orthod, 1987:92 :33-401°Each test cell was removed from the tooth root, cleaned and acid-resistant Birnison. 10 human dental crowns coated with hydroxide and having test windows as detailed above. [Featherstone et al., Caries Res, 1988; 2 2:337-341.

The study was divided into "cold" J legs and "radioactive" legs. radio The "non-radioactive" leg, which had no added tracer, was treated with a test anti-calculus agent (pyrophosphate or and tripolyphosphate) individually have detrimental effects on the true effectiveness of demineralization/remineralization. It was used to determine whether or not it had any effect. In this case, “upper” (against occlusion) The two windows, referred to as the “lower” (to the cervical) and “lower” (to the cervical) was placed on top of the file. 32Pt*potassium birophosphate or sodium tripolyphosphate In the "radioactive" leg with the addition of aluminum, one window of approximately 3 x 7 dragons is placed on the test surface.

The test plan for each 24-hour period was as follows: 1. Inmate teeth were individually and 0.0% acetate. Contains O75mol/L, CaHPO42,0+mol/L It was immersed in 40ml of buffer (pH 4,3) at 37°C for 6 hours every day.

2. Product immersion: Remove the tooth crown from the solution and rinse thoroughly with double deionized water (DDW). DDW of toothpaste (one of the test or placebo products, see below) Individually immersed in 4 mL of medium 1.3 slurry and stirred for 5 minutes on an orbital shaker. . The slurry is refreshed daily and within 30 minutes of cleansing, if desired. cer was added and dispersed by vortexing. After soaking the product, the sample is placed in DDW again. and transferred to remineralization solution.

3. Remineralization Each tooth is then individually calcined to buffer to pH 7.0. Um 1, 5 amol/Ls phosphate 0.9 mmol/LSKCI ( (to maintain ionic strength) 150 mwol/L, cacodylate 20 mmo It was immersed for 17 hours at 37°C in 20+oL of mineralization solution containing l/L. this The solution supports the remineralization phase of the caries process (due to salivary minerals) [te n Cate) and Dui jsters, day and two weeks The test was repeated for 3 weeks including the final period. The test scheme consisted of a total of 6 hours of daily decalcification attacks. , once daily fluoride (or non-fluoride) treatment, and 17 hours of daily remediation ( Remineralization) was planned to be designed.

Test Group The experiment was conducted in duplicate. One group in each set is Using sodium polyphosphate 1.1 uses pyrophosphate. group cross-sectional microhardness test to measure the degree of demineralization. onal m1cro-hardness testing) (see below) Therefore, the four “non-radioactive” legs (hereinafter referred to as A1, A2, and BISB2) were evaluated. ) and tripolyphosphate during treatment with and without fluoride. Radiolabeled salts or pyrophosphates are used to measure the penetration of salts or pyrophosphates into the enamel. 4 identical "using sodium lipolyphosphate or sodium pyrophosphate" Plan to obtain "radioactive" legs (C, , C7, B3, D). The sex leg (hereinafter referred to as E) served as a baseline control and was treated with fluoride ions, tripoly A placebo toothpaste without phosphate and pyrophosphate ions was used.

A. Before remineralization, use of sodium tripolyphosphate/sodium fluoride toothpaste 13 slurry (individually, 4 ml of solution per tooth) before dipping for 5 minutes daily. Demineralization/remineralization cycling.

A2. In duplicate tests, a pyrophosphate/NaF dentifrice was used.

B1 Before remineralization, use sodium tripolyphosphate fluoride-free toothpaste (in A). Similarly, sodium tripolyphosphate is present, but sodium fluoride is added. 1.3 slurry (individually, solution 4+IL per tooth) for 5 minutes daily. Demineralization/remineralization cycling with intersoaking.

B. Birophosphate-containing teeth without fluoride ions in 4 duplicate tests A polish was used as well.

CI Before remineralization, use of sodium tripolyphosphate/sodium fluoride toothpaste 13 slurry (individually, 4+aL solution per tooth) for 5 minutes daily. Ash/remineralization cycling. In this group, radiotracer before dental & soaking Sodium tripolyphosphate at 32p as sodium tripolyphosphate added as Labeled umslurry.

In the C2 duplicate test, pyrophosphate was used; and radiolabeled with 32p.

Dl Before remineralization, add "pt*m+-li" sodium polyphosphate as described above. Added sodium tripolyphosphate dentifrice (sodium fluoride as in C) 1.3 slurry (individually, 4 mL of solution per tooth) of Demineralization/remineralization cycling with daily 5 minute soaking.

B2 In duplicate, pyrophosphate was used and similarly radiolabeled.

E, 1.3 slurry of placebo toothpaste (no added sodium fluoride, tripolitan individually without addition of phosphate or picrate (4 mL of solution per tooth). Demineralization/remineralization cycling with daily 5 minute soaking.

All groups used freshly prepared treatment slurries. Decalcification and relithification The ashing solution was replaced weekly.

demineralization and remineralization solutions were analyzed. After 7 and 14 days of cycling, F- For each individual tube was analyzed. Subtracting the starting value, F - in solution The change was calculated.

Physical analysis 2 groups by cross-sectional microhardness profile as shown below A1, A2, B2 and E were evaluated. Double repeat radiotracer group (C, , C2, D, and B2) clearly could not be evaluated in this way.

They are determined by radiotracer counting as described separately below. evaluated.

After the cycling period, the teeth from groups A, B and E were completely washed in DDW. Clean and section longitudinally through the center of the generated lesion as conventionally detailed. As it is [ten Cate et al., Caries Res, 1985: 19, 335-3411, the exposed cut surface was buried with epoxy resin. I set it. After successive polishing of the impacted tooth, following the method disclosed in the above-mentioned document, Each lesion was evaluated based on cross-sectional microhardness. The indent is , into the intact lower enamel across the sectioned lesion, 25 μm from the dissection plane. It was started and repeated at 25 μm intervals to a depth of 300 μm. This method uses a microphone The results were compared with those of radiography. [White and Featherstone, Caries Res, 1 987:21:502-5121゜Increments according to the formula disclosed by the present inventors The eye length was converted to volume % inorganic and then [Hot] Wight and Featherstone, Caries Res, 1987:21:502 -512, for each lesion on each tooth, use Numbusson's rule for each profile. The mineral loss (ΔZ) value (μ intestine x volume % mineral) was calculated using each group Calculate the average value of △Z for Plotted as depth from surface.

Radiotracer Analysis Teeth from Niger loops C and D were thoroughly cleaned in DDW. , the varnish was removed from each tooth individually by acetone. small pre-weighed For each sample using round/recon carbide paper (600 grade) Eight polishings were performed to remove a layer of pus approximately 5 μ thick. Weigh each sample and Dissolve in Noyon Cocktail and release in a Sarun ntillation counter. The radioactivity was counted.

Sodium tripolyphosphate and in the presence and absence of fluoride The results were compared for pyrophosphate and pyrophosphate products. In other studies, radiotracer The “non-radioactive” leg (A and The amount of lesion formation was measured by B).

Uptake of tripolyphosphate and picrate into caries-like lesions This assay In vitro human experiments with sodium lipolyphosphate or pyrophosphate The uptake of the test substance into preformed caries-like lesions in the namel was evaluated: human molars with caries, with the buccal or lingual surfaces removed (by microscopy) tooth enamel. Clean and condition the teeth as described above for pH cycling studies. Manufactured.

Artificial caries lesion formation, White's method [Caries Res , 1987: 21: 228-2421, in hydroxyapatite. pH 5,0 buffer with 50% saturation and 12% carbobol (0,05 +ool/L lactate) for 5 days. One window (3X7m) on one enamel surface of a molar prepared with the method This caused caries-like lesions.

This system produced lesions approximately 100 μl deep in 5 days.

Soaking in tripolyphosphate or pyrophosphate: removes preformed caries-like lesions. Individually, the teeth were treated with the same concentration as used in the pH cycling test. 32p-labeled sodium tripolyphosphate or tripolyphosphate added in 201 L of 1=3 slurry of sodium lyphosphate or birophosphate dentifrice. Soaked. A group of 10 teeth each was used. The first group is 1 time, the second group was 4 hours, sodium tripolyphosphate and birophosphate Soaked against salt. At the end of the soaking period, the tooth is removed, cleaned in DDW, and immediately Air-dried. They are radiotracers collected using the polishing method described above. I evaluated it accordingly.

Table 6 As the mean value (SD - standard deviation) of each group for the upper and lower windows Relative mineral loss amount ΔZ (volume %xum). The value is the ΔZ value for the upper window Place them in ascending order.

PPi’ toothpaste with A2 NaF” 292 (346) 318 (3 6g) 5TPP with A, Na, F! Toothpaste 597 (425) 2 73 (638) B, S T P P 1300 (814) without NaF 1996 (834) B, P P i without NaF 1399 (652) 2671 (1643)'PPi is potassium pyrophosphate/sodium pyrophosphate (4.0%/1.81%).

"5TPP means sodium tripolyphosphate (5%).

NaF at a concentration sufficient to give '1100 pp++F-.

Sodium tripolyphosphate and potassium/sodium pyrophosphate mixtures are showed a significant reduction in caries compared to placebo, and this abroaching demonstrated by the combination of phosphate and NaF.

Continuation of front page (72) Inventor Matuzza Nobile, Salvatore United States Newspaper 264 Crocker Brace, Howarth, SE 07641

Claims (30)

[Claims] 1. a substantially non-toxic effective amount of a water-soluble pyrophosphate in an orally acceptable carrier; or treating the tooth with a preparation containing a demineralization inhibitor consisting of tripolyphosphate. A method for treating or preventing dental caries by inhibiting enamel demineralization. 2. 2. The method of claim 1, which is a toothpaste or a gel. 3. 3. The method of claim 2, wherein the phosphate is present in an amount of at least 2% w/w. 4. 4. The method of claim 3, wherein the phosphate is present in an amount of at least 5% by weight. 5. A method according to claim 4, wherein the phosphate is a pyrophosphate in the form of an alkali metal salt. . 6. The formulation consists of wetting agents, thickening agents, abrasives, surfactants, pigments, and preservatives. 6. The method of claim 5, which is a toothpaste. 7. The formulation contains 1.8% tetrasodium pyrophosphate and 4.0% tetrapotassium pyrophosphate. 7. The method of claim 6, wherein the toothpaste contains %. 8. the formulation is a toothpaste containing at least 5% by weight of tripolyphosphate; 5. The method according to claim 4, wherein the alkali metal cation is sodium or potassium. . 9. Toothpaste contains humectants, thickeners, abrasives, tetrasodium tripolyphosphate, and interfaces. 9. The method of claim 8, comprising an activator, a dye, and a preservative. 10. 2. The method according to claim 1, wherein the formulation is a gargle. 11. 11. The method of claim 10, wherein the mouthwash contains about 0.5-5% phosphate. 12. The person according to claim 11, wherein the gargle contains an alkali metal salt of tripolyphosphoric acid. Law. 13. Claim 12, wherein the gargle contains about 0.5% sodium tripolyphosphate. How to put it on. 14. 14. The method of claim 13, wherein the gargle contains an alkali metal salt of pyrophosphate. 15. Pyrophosphate is approximately 2.06% sodium pyrophosphate and potassium pyrophosphate. 15. The method of claim 14, wherein the mixture contains about 0.71% um. 16. an orally acceptable carrier and a substantially non-toxic effective amount of water-soluble pylori Contains an enamel demineralization inhibitor consisting of phosphate and tripolyphosphate oral cavity for the treatment or prevention of dental caries in humans by reducing or preventing demineralization. formulations that are acceptable to the public. 17. 17. The formulation according to claim 16, which is a toothpaste or a gel. 18. 18. The formulation according to claim 17, wherein phosphate is present at least 2% w/w. . 19. 19. The phosphate according to claim 18, wherein the phosphate is a pyrophosphate in the form of an alkali metal salt. formulation. 20. Claims consisting of wetting agents, thickening agents, abrasives, surfactants, pigments, and preservatives The formulation according to item 19. 21. Tetrasodium pyrophosphate 1.8% and tetrapotassium pyrophosphate 4.0% 21. The formulation according to claim 20, comprising: 22. 19. The formulation according to claim 18, wherein the phosphate is an alkali metal salt of pyrophosphoric acid. 23. Claims consisting of wetting agents, thickening agents, abrasives, surfactants, dyes and preservatives The formulation described in 22. 24. 24. The formulation of claim 23, containing about 5% sodium tripolyphosphate. 25. 17. The formulation according to claim 16, which is a gargle. 26. 26. The formulation of claim 25, containing about 0.5-5% phosphate. 27. 27. The formulation according to claim 26, which is an alkali metal salt of tripolyphosphoric acid. 28. 28. The formulation of claim 27, containing about 0.5% sodium tripolyphosphate. . 29. 14. The formulation according to claim 13, containing an alkali metal salt of pyrophosphoric acid. 30. Pyrophosphate is approximately 2.06% sodium pyrophosphate and potassium pyrophosphate. 15. The formulation according to claim 14, which is a mixture of 0.71% um.