DE2126539A1 - Oral care products - Google Patents

Description

2126533

Colgate-Palmolive Company. New York (NY, USA)

Oral care products ******************

The present invention relates to customer care products, ie products which are suitable for use in the oral cavity, for example toothpastes and toothpastes, tooth powder and liquid dentifrices, mouthwashes, mouthwashes, dental chewing gum, tablets, lozenges and coated tablets.

According to the invention, such an oral care agent contains a non-toxic polymeric amino-cyano-diguanide or a salt thereof as an antibacterial3 agent, as well as a diluent or a carrier for the antibacterial agent

109851/1823

BATH ORIGINAL

Means and for other active ingredients, if any are present..

The polymeric amino-cyano-diguanides are more cationic Natural, but with anionic substances and other substances that are generally contained in oral care products are compatible, for example wetting agents, fluorine-releasing compounds and, if the oral care product, for example a toothpaste, a sparingly soluble polishing material contains, with that portion of the polishing material which is water-soluble or saliva-soluble.

The polymeric amino-cyano-diguanide, which is present in one embodiment of the invention, can, for example, according to the method according to British patent no. 1,152,243 are produced? then hexamethylenediamine, H ₀ N (CH ₀ LNH ₀ , or one of its inorganic

c. d b d

Chemical salts with the hexamethylenediamine salt of a dicyanimide of the formula (HJMCH ₀ L-NHJ. (N (CN) ₀ ). For example, at least at the beginning of the reaction one works in the presence of a hydroxyl-containing solvent such as an aliphatic alcohol with 1 to 3 4 carbon atoms, but preferably The solvent containing hydroxyl groups can be mixed with a small amount of a solvent free of hydroxyl groups, such as toluene.

109851/1823

BATH ORIGINAL

premix to about 6 to 8 wit by means of a mineral acid hydrochloric acid, which überfuhrt the free diamine in the acid-addition salt, and nan the solution heated initially to about 10O ⁰ C under atmospheric pressure, at least • inen part of the hydroxyl group-containing solvent "and remove. The reaction mixture is then heated to about 120 ° C. to 170 ° C. for about 1 to 8 hours. If desired, water can be added during cooling. The amino-cyano-polydiguanide obtained in this way can then be separated from any water-immiscible solvent which may be present and, if wished, can also be isolated from the aqueous solution.

The polymeric product is a mixture of polymers of the formula

Y {- - NH-C-NH-C-NH- (CH

NH NH

wherein Y is HN (CH ₀ ), - or

C C. O

N 5 C-NH-C-NH ₀ (CH,) - c b

and X for -NII or

- NH-C-NH-C = N

You

and η denotes a small whole number (for example from 2 to 6, the mean value of η in the mixture

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• ♦ »* it

• »

is about 4).

The average molecular weight of the polymers produced in this way is generally around 1100.

As already indicated, non-toxic addition salts of such compounds can be used. Such salts can be inorganic, for example the fluorides, chlorides, nitrates or sulfates, or they are organic such as the succinates, tartrates, citrates, maleates or metbsulfates.

Some addition salts are insoluble, such as the water-insoluble addition salt of the
Sulfuric acid. Such salts can be found in discrete form
Introduce particles into dentifrices, with the particles on the surface of opaque toothpastes or inside and on
the surface of clear, ie transparent or translucent gels can be visible.

The polymeric product preferably used is a mixture of different combinations of the meanings of the symbols X and Y and different amounts of repeating units of the formula

-NH-C-NH-C- (CHJ ₁ .-

Il Il ²⁶

NH NH
In particular, the polymeric product is called chloride

produced and mainly containing the linear amino

109851/1823

kit ^ <^ <ψ * ι V-Γ 2126533

cyano-polyhexamethylene diguanide of the formula

H ₂ M (CH ₂ ) ₆ - [HH-C-NH-C.NH- (CH ₂ ) ₆ ] ₄ -ilH-C- NH ♦ C m *

Il ι ι

NH NH + Cl. NHJ Cl

This polymer is readily soluble in water and saliva and is characterized by an _{increased antibacterial effectiveness compared to 1 f} 6-di- (p-chlorophenylbiguanidohexane).

The polymer can generally be used in amounts of 0.01 to 5 $, preferably 0.05 to 1.556, based on the Weight of oral hygiene product to be used.

In certain embodiments of the invention, the oral care product can be liquid, for example a mouthwash or mouthwash. In such agents, the carrier is generally a mixture of water and alcohol. The weight ratio of water to alcohol is usually 1: 1 to 20: 1, preferably 3: 1 to 20: 1, in particular about 17: 3. $ The total amount of V / ater and alcohol in this type of care agent generally ranges between 70 wt. And 99.95 wt.% Of the composition. The pH of such liquid agents is usually between 4.5 and 9, in particular between b.5 and 8.

Such liquid oral care products can also contain a wetting agent and / or a fluorine-releasing compound

- 5 109851/1823. '

• ♦ ·

dung included. 2126539

In certain other embodiments of the invention the oral care product has a solid or pasty nature, for example as tooth powder, toothpaste or Toothpaste. The carrier contains such solid or pasty customer care products, a polishing material.

Examples of such polishing materials are water-insoluble

Sodium metaphosphate, potassium metaphosphate, tricalciuraphos- ' phate, dicalcium phosphate dilute hydrate, anhydrous dicalcium phosphate, Calcium pyrophosphate, magnesium orthophosphate, Tri-magnesium phosphate, calcium carbonate, clay, aluminum silicate, Zirconium silicates, silica, plastics such as polymethyl methacrylate, bentonite and mixtures of these substances. Preferred polishing agents are crystalline silica with particle sizes up to 5 microns, a medium one Particle size up to 1.1 microns and a specific surface area up to 50,000 cm / g, insoluble sodium metaphosphate, anhydrous dicalcium phosphate and calcium carbonates which are usually so finely divided that they are medium Have a valley size less than 10 microns.

Alumina, especially the hydrated alumina marketed by Alcoa under the designation "C333" and an alumina content of 64.9 wt. ^, a silica gel

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halt of 0.008 wt. 56, e ^ NEN iron oxide content of 0.003% and a water content of 0.37 # at 110 C, a apeeifi ULTRASONIC weight of 2.42 and a particle size such that lOOjS of the particles less than 50 microns and 84 i " The particles are smaller than 20 microns" is most preferred.

If you use practically clear gels, is a

Polishing agents made from colloidal silica, for example "Syloid 72" and "Syloid 74" or "Santocel 100" and complexes Alkali fainosilicates are particularly useful because these materials have indices of refraction that are close to the refractive indices of the gelling agent-liquid system commonly used in dentifrices (Water and / or humectant).

Many of the so-called "water-insoluble" polishing agents are anionic in character and contain small amounts of soluble substances. For example, insoluble sodium metaphosphate can be produced, for example according to Thorpe's Dictionary of Applied Chemistry, Vol. 9 (4th edition), pages 510 to 511. The insoluble sodium metaphosphates known as Madrell's salt and Kurrol's salt are further examples of suitable substances. These metaphosphates show only a very low solubility in water and are therefore generally referred to as insoluble metaphosphates.

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net. They contain small amounts of soluble phosphates as impurities, usually a few percent up to 4 wt. ^. The amount of soluble phosphates that are believed to be is a soluble sodium trimaphosphate in the case of the insoluble sodium metaphosphate, can, if desired, can be reduced by washing out with water. Insoluble alkali metaphosphates are generally in the form of

Powders used with a particle size such that no more than 1 % of the substance is larger than 37 microns.

The polishing agent is generally present in amounts between 20% and 99% by weight of the oral hygiene product. Preferably, a toothpaste 20 to 75 fo and a tooth powder 70 to 99%.

To produce tooth powders, it is usually sufficient for example by grinding the various solid ingredients in the desired amounts and with the to mix desired particle sizes.

In paste-like oral care products, the antibacterially effective diguanide polymer is compatible with the Polishing agents and the other components of the care agent. For example, a toothpaste can have water as the liquid carrier, generally in quantities between 10 and 90% by weight of the agent. As a humidifier

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agents or binders can be glycerin, sorbitol or Propylene glycol also be present. Particularly preferred liquid components are mixtures of water, Glycerin and sorbitol.

In clear gels where the refractive index is particularly important, is preferably used about 10 to 30 wt.% Of water, 0 to about 80 wt. ^ Glycerin and about 20 to 80 wt. # Sorbitol. Natural or synthetic gums or substances similar to guiruni such as Irish moss, sodium carboxymethyl cellulose, methyl cellulose or hydroxyethyl cellulose can be used as the gelling agent. Other useful gelling agents include synthetic inorganic siliceous clay (trademarks "LAPONITE CP" and "LAPONITE SP") having the formula [Si ₃ Mg ₅ ^^^ H ₇ ^ O ₃₄ ] ° ⁶ NaJ ^, tragacanth, polyvinylpyrrolidone and starch. In toothpastes, these are usually used in amounts up to 3. at 10% by weight, preferably in the range from $ 0.5 to $ 5. The preferred gelling agents are methyl cellulose, hydroxyethyl cellulose, "LAPONITE CP" and especially "LAPONITE SP". In a toothpaste or gel, the liquids and solids are proportioned in such a way that a creamy or gelatinous mass is obtained, which is made up of a pressure

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container or from a deformable tube, for example made of aluminum or lead, can be extruded.

The solid or pasty oral care products can also contain a surface-active agent and / or a fluorine-releasing compound.

Usable surfactants (wetting agents) are organic substances and show an increased prophylactic

see effectiveness. They facilitate thorough and complete dispersion of the care product in all parts of the oral cavity. The organic wetting agents can be anionic, nonionic, ampholytic or cationic in nature, and the wetting agent used is preferably a cleaning material which gives the care agent a cleaning and foam-forming property. Such cleaning agents are water-soluble salts of higher fatty acids of the monoglycerides Kor.osulfa- th, for example the sodium salt of monosulfonated monoglyceride of fatty acids derived from hydrogenated coconut oil; higher alkyl sulfates such as sodium lauryl sulfate; Alkyl aryl sulfonates such as sodium docecylbenzenesulfonate; higher alkyl sulfoacetates; higher fatty acid esters of 1,2-dihydroxypropanesulfonates; and practically saturated higher aliphatic acylamides lower aliphatic acher aminocarboxylic acids, for example those with 12 to

- 10 109851/1823

At

16 carbon atoms in the fatty acid, alkyl or acyl radicals. Examples of the last-mentioned amides are N-lauroyl sarcosine and the sodium, potassium and ethanol amide salts of N-lauroyl, N-myristyl or N-palmitoyl sarcosine. These Substances should be practically free from soaps or similar, be higher fatty acid-containing substances, which have a tendency to reduce the effectiveness of these compounds. The use of the mentioned sarcosinates in dental care products according to the invention is very special advantageous because these compounds have a significant and long-lasting effect in preventing acid formation in the oral cavity, which is due to the breakdown of carbohydrates and because they also have the Decrease the solubility of the tooth enamel in acidic solutions

Nonionic surface-active agents which can be used are, for example, condensates of Eorbitannonostearat with about 60 mol parts of ethylene ^{oxides (eg '1} WEENS ") condensates of ethylene oxide with propylene oxide condensates of propylene glycol ( ⁿ PLURONICS") and amphoteric substances such as quaternized imidasole derivatives, which are sold under the name ¹¹ MIRANOL "Eg" MIRANOL CM "are commercially available. Cationic, surface-active germicides and antibacterial agents can also be used

effective compounds such as di-isobutylhenoxyethoxyethyl

- 11 -109851/1823

dimethylbenzylammonium chloride, benzyldimethylstearylammonium chloride, tert. Amines with one fatty alkyl group (12 to 18 carbon atoms) and two (or more) on nitrogen bonded oxyethylene groups (usually with 2 to 50 ethanoxy groups per molecule) and salts with acids and compounds the structure

R-N-CH CH CH N:

(CH ₂ CH ₂ O) H

where R is a fatty alkyl group with 12 to 18 carbon atoms and x, y and ζ together are at least 3, as well as their salts with mineral acids or organic acids are used. Preferably, 0.05 to 5 wt. $ of the surface-active Substance in the oral care products.

In certain embodiments of the subject matter of the invention a fluorine-releasing compound is present. These compounds can have poor water solubility have or be completely water-soluble. They are characterized by the ability to convert fluoride ions into water dispense and with other ingredients dos oral care products not to respond. These substances include inorganic fluorides such as suitable alkali,

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Alkaline earth and heavy metal salts, for example sodium

*
fluoride, potassium fluoride, ammonium fluoride, lead xuoride , copper (I) fluoride, zinc fluoride, tin fluorides such as tin (IV) fluoride or tin (II) chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, sodium monofluorophosphate, aluminum monofluorophosphate, fluorinated sodium calcium pyrophosphate and sodium fluorozirconate. Preference is given to using alkali and tin fluorides, for example sodium or tin (II) fluoride and mixtures thereof.

The amount of fluorine-releasing compound depends to some extent on the type of this compound, its solubility and the type of oral care product, but it must be a non-toxic amount. In solid oral care products such as toothpastes or tooth powders, it is assumed that such an amount of such compounds gives satisfactory results that at most 1% by weight, based on the product, of fluoride ions gives off. Suitable minimum amounts of such compounds can of course be used, but generally such amounts of compounds will be added as will be 0.05. Release up to 1 %, preferably about 0.1 wt. #, of fluoride ions. In the case of alkali fluorides and tin (II) fluoride, for example, up to% by weight thereof are present, based on

- 13 109851/1823

on the care product, preferably in the range from 0.05 to 1% by weight . In the case of sodium monofluorophosphate, the amount of this compound can be up to 7.6% by weight, for example 0.76 %.

In liquid oral compositions such as mouth detergents are generally those amounts of fluorine-donating compounds that up to 0.13%, preferably 0.0013 to 0.1% and in particular # 0.0013% bi3 0.05> released at $ fluoride ions, based on the weight of the agent.

Certain embodiments of the subject matter of the invention can be used in addition to the amino-cyano-diguanide polymer Contain antibacterial agents, with a total of about 5 wt \ # of antibacterial agents are achieved. Such additional funds are, for example:

1 5

N - (4-chlorobenzyl) -N - {2,4-dichlorobenzyl) biguanide; p-chlorophenyl biguanide; 4-chlorobenzhydryl biguanide; 4-chlorine

5 benz- ~ hydrylguanylurea; N-3-lauroxypropyl-N-p -chlorobenzyl biguanide; 1,6-di (p-chlorophenylbiguanidohexane); 1- (Lauryldimethylanmoniuin} -8- {p-chlorobenzyldimethylaramoniuin) -octane dichloride f 5, e-dichloro-2-guanidinobenzimidazole; N p -chlorophenyl-N -laurylbiguanid; 5-amino-1,3-bis (2-ethylhexyl) -5-methylhexahydropyramidine; and their non-toxic acid addition salts, especially those in which the anion

- 14 109851/1323

has a fluorine atom like fluoride, monofluorophosphate, Hexafluorosilicate and hexafluoroaluminate. That is preferred Dihydrogen fluoride. A very preferred compound is 1,6-di (p-chlorophenylbiguanidohexane) dihydrogen fluoride.

In general, the amount of antibacterial agents in the oral care product is 0.01% by weight to 5% by weight, and the predominant portion, i.e. more than 50% by weight of the antibacterial agent is preferably the amino-cyandiguanide polymer, with the additional antibacterial agent making up the minor component.

The oral care products according to the invention can contain numerous other substances. Examples are colorants or lightening agents, preservatives, Silicones, chlorophyll compounds and substances containing ammonia such as urea, diammonium phosphate and their mixtures. These additives, if they are present, are added to the care products in such amounts that the properties and do not significantly affect the character of the means.

Suitable flavorings or sweeteners can also be present. Examples of suitable flavorings are aromatic oils such as Pf efforminzöl, spearmint oils , Gaultheria, Saxifraga, clove, eucalyptus, marjoram,

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109851/1823. ^ ₀ original

'' Cinnamon, lemon and orange and sodium methyl salicylate. Suitable sweeteners are sucrose, lactose, maltose, sorbitol, sodium cyclamate, perillartin and saccharin. Such flavorings and sweeteners can together make up about 0.01 to 5 wt. # Or more of the care product.

When making toothpastes, one removes Usually enclosed air bubbles from the product by venting under vacuum, especially towards the end

. the production. In practicing the present invention it was observed that in clear · dental care gels more suitable Viscosity, the immobile air bubbles dispersed in it have a beneficial effect on the appearance of the toothpaste and accordingly they can remain in it. The air can also be replaced by another gas in non-toxic quantities be replaced, for example by nitrogen or carbon dioxide. In particular, carbon dioxide can cause toothpaste give a foaming character.

If one wishes to have as little air as possible in the toothpastes according to the invention, the "Uniraix ¹¹ apparatus, which is described in" Process Engineering ", 9/11/1970, pp. 81 to 85, is particularly suitable for this purpose This apparatus can be made to rotate a mixing tool clockwise or counterclockwise, and the effect of the mixing tool is through the effect of a

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t Ir

Leaf scraper added, Vfelcher serves the work surface of the device to scrape in. A plastic such as polytetrafluoroethane is preferably used as a scraper, because it is compatible with the individual components of the toothpaste. The arrangement of the mixing tool and of the scraper on a column towering in the middle of the apparatus and the presence of a hydraulically moved one Vacuum tight lid ensures that little 'air is trapped in the manufacture of the formulation will. In this way, a gelling agent and part of the liquid can be made up of water and / or humectant mix with a good result in the Unimix apparatus. Then mixed the remaining water and the other liquids are separated with the polishing agent and the other additives (with the exception of substances to be added later such as aromatic oils) in the Unimix and then combines the two dispersions again in Uniraix. If desired, ir.an can remove most of the small amount of trapped air,

Under ^

by putting the apparatus under pressure. The apparatus permits the mixing of ingredients at room temperature and also at higher temperatures.

The following examples illustrate the invention. The ingredients are mixed together in the usual way mixed. Percentages relate to weight.

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109851/1823

The polyr.ere diguanid was produced according to the process as described in British Patent No. 1,152,243.

Example 1: Mouthwash

Ethanol Mouthwash Ethanol - 18 - 15.0 "PLURONIC 75" Glycerin 109851/1823 0.5 Sodium fluoride Sodium monofluorophosphate 0.05 polymeric diguanide polymeric diguanide 0.1 Sodium saccharate "TWEEN 80" 0.2 Flavor / color Sodium Saccharate 1.0 water Flavor / color to 100.0 Example 2: water 4.0 1.0 0.2 0.5 0.5 0.2 1.0 to 100.0

21265Ϊ?

BeianSiel 3:.

toothpaste

hydrated clay toothpaste *
55.0 Glycerin 20.0 Hydroxyethyl cellulose 1.0 "MIRAKOL C ₂ K" 1.0. 1,6-di-p- (chlorophenylbiguanido-
hexane) 0.20 polymeric diguanide 0.25 Sodium saccharate 0.2 Flavoring agent 1.0 water to 100.0 Example 4:

Dicalcium phosphate dihydrate 40.0

Calcium carbonate (precipitated) 8.0

Glycerin. 10.0

Sorbitol ($ 70 ig) 12.0

Sodium N-lauroyl sarcosinate 2.0

Carboxymethyl cellulose 0.9

Sodium benzoate 0.2

Tetrasodium pyrophosphate 0.5

Sodium saccharate 0.2

- 19 -

108851/1823

Flavor 1.0

polymeric diguanide 0.5 water to 100.0 Example 5;

Toothpaste .

crystallized silica 20.0

Polymethyl methacrylate 20.0

Glycerin. 20.0

Sodium lauroyl sulfate. 2.0

Hydroxyethyl cellulose 1.0

Sodium fluoride 0.1

polymeric diguanide 0.5

Sodium saccharate 0.2

Flavor 1.0 Waseer to 100.0 Example 6;

toothpaste

insoluble sodium metaphosphate 45.0

Glycerin 6.0

Sorbitol 16.0

Sodium N-lauroyl sarcosinate 2.0 Sodium monofluorophosphate 0.8

- 20 -109851/1823

toothpaste 2126539 • Calcium carbonate (calcite) * polymeric diguanide Calcium carbonate (aragonite) 0.5 Hydroxyethyl cellulose Glycerin 1.0 Sodium saccharate "PLURONIC 75" 0.2 Flavoring agent polymeric diguanide 1.0 water to 100.0 Example 7: 20.0 25.0 20.0 1.0 0.25

1,6-di-p- (chlorophenyl-

biguanidohexane) 0.20

Sodium saccharate 0.2

Sodium carboxymethyl cellulose 1.0

Water . to 100.0

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Claims (1)

2146539 ι * Patent claims 1. Oral care products, characterized by a content of einöm non-toxic amino-cyano-diguanidpclymer or a salt thereof as an antibacterial agent and of a carrier that is compatible with this agent. 2. Oral care product according to claim 1, characterized in that the antibacterial agent is a mixture of polymers of the formula γ [ NH-C-NH-C-NH- (CH ₀ ). ] X - do n NH NH wherein Y has the formula H ₀ N- (CH ₀ ) _c - or d CD N s C-NH-C-NH (CH _O ) _C d ο NH X has the formula -NH "or -NH-C = NH-CN and η a ² NH denotes an integer from 1 to 6, or represents salts thereof. .3. Customer care product according to claim 2, characterized in that the polymer mixture has the following main form: H ₀ N (CH ₀ ) _c - [NH-C 1 _{-C 4} -NH- (CH 0).] ~ NH-C KH -C = N. 2 2 6 - _M 2 6H j, - NH NH ₂ Cl NH ₀ Cl 4. Oral care agent according to claim 1 to 3, characterized marked that 03 the polymer antibacterial - 22 -109851/1823 BAD ORiGINAL Contains agent in amounts of about 0.01 to 5 wt. $ 5. 5. Oral care product according to Claims 1 to 4, characterized in that the carrier is a mixture of water and alcohol in a weight ratio of about 1 to 20: 1 and that the oral care product contains an oral wash iet. 6. Oral care products according to Claims 1 to 5, characterized in that the carrier also contains a fluorine-releasing compound. 7. Oral care product according to claim 6, characterized in that that the fluorine donating compound is sodium fluoride. 8. Oral care product according to claim 6, characterized in that that the fluorine-releasing compound is tin (II) fluoride. 9. Oral care product according to claim 6, characterized in that the fluorine-releasing compound is sodium monofluorophosphate is. 10. Oral care agents according to claim 5 to 9, characterized characterized in that the carrier further contains a surfactant. 11. Oral care product according to claim 10, characterized in that indicates that the surfactant is an anionic Is wetting agent. - 23 - 109851/1823 ^{BATHROOM 0RIGINAL} - 12. Oral care product according to claim 11, characterized in that that the anionic wetting agent is sodium lauryl sulfate is. 13. Oral care product according to claim 11, characterized in that the anionic wetting agent is sodium N-lauroyl sarcosinate is. 14. Oral care products according to claims 1 to 3 4, characterized in that the carrier material is a solid
Contains water-insoluble paint, the oral care product is a toothpaste. 15. Oral care product according to claim 14, characterized in that the polishing agent is insoluble sodium metaphosphate is. 16. Oral care product according to claim 14, characterized in that the polishing agent contains dicalcium phosphate. 17. Oral care products according to claims 14 to 16,
characterized in that the carrier material also
contains a fluorine-releasing compound. 18. Dog care product according to claim 17, characterized in that that the fluorine-releasing compound is sodium fluoride. 19. Oral care product according to claim 17, characterized in that the fluorine-releasing compound tin (H) - - 2 * - ^109861/1823 BADOR ₁ Q ₁ NAt is. 20. Oral care product according to claim 17, characterized in that the fluorine-releasing compound is sodium monofluorophosphate is. 21. Oral care product according to claims 17 to 20, characterized in that the carrier substance furthermore a contains surfactant. 22. Oral care product according to claim 21, characterized in that that the surfactant is an anionic wetting agent. 23. Oral care product according to claim 22, characterized in that that the wetting agent is sodium lauryl sulfate. 24-. Oral care products according to claim 22, characterized in that that the wetting agent sodium N-lauroyl sarcosinate is. 25. Oral care products according to claims 1 to 24, characterized in that it further contains an additional antibacterial agent which is related to of said polymer is present in a smaller amount and that the total amount of antibacterial Average is about $ 0.01 to $ 5 wt. 109851/1823 ORIGINAL BATHROOM