CN1093756C

CN1093756C - Oral preparations

Info

Publication number: CN1093756C
Application number: CN96102595A
Authority: CN
Inventors: C·D·吉斯
Original assignee: Unilever PLC
Current assignee: Unilever PLC; Unilever NV
Priority date: 1996-01-31
Filing date: 1996-01-31
Publication date: 2002-11-06
Anticipated expiration: 2016-01-31
Also published as: CN1156022A

Abstract

The present invention relates to an oral preparation having activity of preventing decayed teeth. The composition comprises pyruvic acid or salt accepted by oral cavity, urea and/or arginine or derivatives thereof. The mixture can make the pH value of the bacterial spot increased.

Description

Oral preparations

The present invention relates to oral preparations, particularly relate to and have the active oral preparations of anti-dental caries tooth.

People know that multiple water solublity fluorochemical can be used for anti-dental caries tooth.Example has sodium monofluorophosphate, sodium fluoride and stannic fluoride.

Now existing people advises using the anti-dental caries tooth of composition for oral cavity of not fluorine-containing medicine.One of method of anti-dental caries tooth is that the pH of bacterial plaque is raise, and perhaps cushions bacterial plaque pH.For this reason, the someone advises carbamide is used in (J.Am.Dent.Assoc.49, (1954), 185-190 page or leaf) in the composition for oral cavity.Equally, the someone advises with arginine buffering bacterial plaque pH and produces the effect (US-A-4,154,813) that pH raises.

We find when searching makes the other drug that bacterial plaque pH raises: when acetone acid or its salt and S.mutans FA-1 and Lactobacillus acidophilus (Lactobacillus acidophillius) and the mixture that contains the oral cavity bacterium of salivary deposits system were mixed, acetone acid or its salt had pH rising effect.

In numerous other medicines, JP-A-59/029618 proposes acetone acid as anti-dental caries tooth medicine.According to the document, acetone acid has antimicrobial activity to the S.mutans in the oral cavity.Disclosure is not seen in pH rising effect.Surprisingly, we have now found that, the acceptable salt of acetone acid or its oral cavity cooperate with carbamide and/or arginine can produce add and the pH cushioning effect.

Therefore, the present invention relates to have the active oral preparations that comprises acetone acid or its acceptable salt in oral cavity of anti-dental caries tooth, it is characterized in that it also comprises carbamide and/or arginine.

The acceptable salt in the oral cavity of acetone acid is alkali metal salt, for example sodium salt and potassium salt.Other suitable salt are lithium salts, magnesium salt, calcium salt, strontium salt, mantoquita, zinc salt, pink salt, lanthanum salt, ytterbium salt, scandium salts, europium salt.

Acetone acid or its salt consumption in the present invention in 1-50% (weight) scope, preferred 2-25% (weight), more preferably 5-10% (weight).

Arginine consumption in the present invention is generally 1-50% (weight), preferred 2-25% (weight), preferred especially 5-10% (weight).The consumption of carbamide is generally 1-20% (weight), preferred 1-10% (weight).Can also use carbamide and arginic derivant, for example sialin has 2-4 amino acid whose small peptide, one of them is the arginine of AA-arg type and arg-AA type, and wherein, AA is a glycine, leucine, isoleucine, tyrosine, serine (is seen US-A-4,154,813) with according to US-A-4,477,429 following formula: compound:

CH ₃(CH ₂) yNH-CH (COOH)-(CH ₂) ₃-NH-C-(: NH)-NH ₂(wherein y=6-29), for example N-α-octyl group arginine and N-alpha-decyl arginine.

According to the form of oral cavity with product, oral cavity of the present invention will be contained acetone acid or its salt and carbamide and/or arginine and well known to a person skilled in the art other conventional ingredients with product.For example, if the oral cavity product of clean one's teeth cream or paste form, then this product should comprise the liquid phase that contains wetting agent and this granular solids abrasivus can be remained on binding agent or thickening agent in this liquid phase with the steady suspension form.Surfactant and flavouring agent also are the spendable compositions of commercial acceptable dentifrice.

Wetting agent commonly used is glycerol and sorbitol syrups (containing about 70% solution usually).Yet other wetting agent is known for those skilled in the art, comprises propylene glycol, lactitol and hydrogenated corn syrup.The content of wetting agent is generally in 10-85% (weight) scope of about dentifrice weight.The remainder of described liquid phase will mainly be made up of water.

Equally, multiple binding agent or thickening agent have been specified and have been used in the dentifrice, preferably sodium carboxymethyl cellulose and synthesising biological polymeric gel.Other binding agent comprises natural gummy binding agent for example tragakanta, karaya and arabic gum, chondrus ocellatus Holmes, alginate and carrageenans.Silicon dioxide thickening agents comprises white carbon and various sedimentary silicon dioxide.Can use binding agent and mixtures of thickening agents.Binding agent and the thickening agent content in dentifrice is generally between 0.1-10% (weight).

Usually comprise surfactant in the dentifrice, the document has disclosed multiple suitable material again.Widely used surfactant is a sodium lauryl sulfate in the reality, dodecylbenzene sodium sulfonate and sodium N-lauroyl sarcosinate.Other anion surfactant exists with the amount of the 0.5-5% (weight) of dentifrice weight usually.

Usually be used in those aromatic that aromatic in the dentifrice is based on the oil of Herba Menthae Rotundifoliae and lavender.The example of other available fragrance matters has Mentholum, Flos Caryophylli, Ilicis Purpureae, Eucalyptus and aniseed.The amount that dopes the aromatic in the dentifrice is preferably the 0.1-5% (weight) of dentifrice weight.

The composition for oral cavity of the present invention amount of 60% (weight) at the most contains for example silicon dioxide of abrasivus, aluminium oxide, hydrated alumina, calcium carbonate, anhydrous dicalcium phosphate, Tri-Compress, water-insoluble Polymeric sodium metaphosphate., calcium pyrophosphate, hydroxyapatite etc.

Composition for oral cavity of the present invention can comprise multiple optional composition.They comprise ascoxal, for example Antimicrobe compound such as hibitane or 2,4,4 '-three chloro-2 '-hydroxy diphenyl ether, or zinc compound (referring to EP-A-161,898); The tartar composition, condensed phosphate for example, as alkali metal pyrophosphate salts, hexametaphosphate (hexametaphosphate) or polyphosphate (referring to US-A-4,515,772 and US-A-4,627,977) or zinc citrate (referring to US-A-4,100,269); Sweeting agent, for example glucide; Opacifier, for example titanium dioxide; Antiseptic, for example formalin; Coloring agent; Or the pH controlling agent, for example acid, alkali or buffer agent are as benzoic acid.Can also comprise biomolecule, for example enzyme, bacteriocin, antibody etc., and bleaching and brightening agent, for example peroxide.

Compositions of the present invention can also comprise the agent of additional anti-dental caries tooth, sodium fluoride for example, sodium monofluorophosphate, tin bifluoride, calcium glycerophosphate, sodium trimetaphosphate, casein and casein derived thing etc.

Discussion more fully for the preparation composition for oral cavity can be referring to Harry ' sCosmeticology, and the 7th edition, 1982, J.B.Wilkinson and R.J.Moore edit, the 609-617 page or leaf.

The following example illustrates the present invention.Percent and umber are all by weight.

The mixture of anti-dental caries tooth of the present invention agent can also be contained in and be used for alleviating/food of pre-preventing decayed tooth tooth.

Embodiment 1

Salivary deposits experiment press Kleinberg at Arch.Oral Biol., the 28th volume, and 11, (1983), the identical method of reporting in the 1007th page is carried out.

Before experiment, make personnel's fasting that two windings are investigated and prevented oral hygiene 12 hours.Collecting 15ml then stimulates the saliva that produces and places the centrifuge tube of weighing.Centrifugally go out deposit and with twice of KCl solution washing.With its KCl solution dilution with same weight, and 37 ℃ of cultivations 3 hours.

All solution all is adjusted to pH7 and mixes.Then deposit is also transferred to pH7, it is added in the mixture of solution then.Measured the pH of solution then at 0,15,30,45,60,90,120,150,180 and 210 minute.Then data are marked and drawed on the pH-time diagram.The ultimate density of solution: KCl 135mM

Glucose 2.8mM

Acetone acid 33mM

Arginine 33mM

The amount of carbamide solution that 1.5mM adds: glucose 20 μ l

Test 100 μ l

Deposit 500 μ l

KCl 2.48ml, 2.38ml or 2.28ml

(according to the amount of added testing liquid)

For the solution that contains acetone acid and other drug, add 100 each solution of μ l so that ultimate density is identical.

Reduce if need guarantee big pH, add excessive glucose after 30 minutes.

The gained result is as follows:

Time (minute)	Water	Acetone acid	Arginine	Carbamide	Acetone acid+arginine	Acetone acid+carbamide
Time (minute)	Water	Acetone acid	Arginine	Carbamide	Acetone acid+arginine	Acetone acid+carbamide	0	7.32	7.32	7.40	7.33	7.44	7.36
15	6.75	6.67	6.88	7.12	6.77	6.99	0	7.32	7.32	7.40	7.33	7.44	7.36
15	6.75	6.67	6.88	7.12	6.77	6.99	30	6.61	6.67	6.79	6.95	6.72	6.99
45	6.42	6.58	6.71	6.91	6.68	6.97	30	6.61	6.67	6.79	6.95	6.72	6.99
45	6.42	6.58	6.71	6.91	6.68	6.97	60	6.40	6.67	6.65	6.88	6.73	6.91
90	5.72	6.39	6.39	6.56	6.59	6.78	60	6.40	6.67	6.65	6.88	6.73	6.91
90	5.72	6.39	6.39	6.56	6.59	6.78	120	5.36	6.30	6.28	6.40	6.63	6.70
150	5.25	6.23	6.30	6.50	6.57	6.72	120	5.36	6.30	6.28	6.40	6.63	6.70
150	5.25	6.23	6.30	6.50	6.57	6.72	180	5.33	6.22	6.59	6.58	6.62	6.68
210	5.35	6.14	6.83	6.71	6.73	6.71	180	5.33	6.22	6.59	6.58	6.62	6.68

Fig. 1 and 2 represents these data.

Claims

1. one kind has the active oral preparations that comprises acetone acid or its acceptable salt in oral cavity of anti-dental caries tooth, and it is characterized in that: it also comprises carbamide or derivatives thereof and/or arginine or derivatives thereof.

2. according to the preparation of claim 1, it comprises the acceptable salt of 1-50 weight % acetone acid or its oral cavity and 1-20% weight carbamide or derivatives thereof and/or 1-50 weight % arginine or derivatives thereof.

3. according to the preparation of claim 2, it comprises the acceptable salt of 5-10 weight % acetone acid or its oral cavity and 1-10 weight % carbamide or derivatives thereof and/or 5-10 weight % arginine or derivatives thereof.

4. the application of the mixture of acceptable salt of acetone acid or its oral cavity and carbamide and/or arginine or carbamide and/or arginic derivant in the agent of the anti-dental caries tooth of preparation.