DE2158102A1 - Tooth cleaning agent containing 1,6-di- (p-chlorophenyl-biguanido) -hexane - Google Patents

Description

op ^ nittel with content of 1 ₃ 6-di- (p-chlorpheny! -biguanid ο) -hoxan

The Krfindunp; concerns ZabnreinipunPisriittel with a salary of 1,6-di (p-chlorophenyl "bicuanido) hexane.

3 j6-Di- (p ~ chlorphonyl-bi, ^ uanido) -hexane is a well-known antibacterial compound, the particular also prevents the growth of Lactobacillus acidophilus odontolyticus and is therefore recommended as an additive to dental care products has been. The use of this compound in dental care ^ eTnitr.eln therefore leads to a reduction in tooth decay and the Bela

If the compound is used in the form of the free base or in the form of water-soluble salts, such as diacetate or dipyluconate, this leads to unpleasant side effects, in particular to the formation of brown spots on the tooth surface ] ζ and zn a bitter taste of the teeth cleaning · / "ΐ χ η <· ; jmi 11 ο 1 s,

209823/1 171

The invention therefore pertains to the task of round, a tooth cleaning runner with a content of 1,6-di- (p "chlorophenyl-biguanide ) -hexane, which does not have these side effects up; eist.

To solve the problem, it is proposed to use Zahnreinif-unnsir.it toi to use the ar-n content of 1, C-Di- (p-ehlorphenyI ~

as a water-insoluble salt biguanide? ) -hexane / in menr.en from 0.01 to 5 wt. 3, beguile the free base. The inventions of the teeth do not lead even with repeated Oc-use a flake formation on the teeth and lead due to their Insolvency also does not lead to a urianp-enehnen taste of the Preparation. Surprisingly, it was found that this Compounds in spite of their insolubility an excellent anti develop bacterial effectiveness.

^ To the water-insoluble salts of 1,6-di- (p-chlorophore; yl-bißuanido) -hexane include monomeric salts that contain monomeric anions and monomeric cations, such as dihydrogen chloride, Dihydrogen bromide, dihydror.eniodide, disaccharinate, Disarcosinate or dibenzoate, and also salts, which appear to have a polymeric structure, and the polyvalent ones Contain anions, such as the salts of weak acids such as phosphates, citrates, malates, tatrates and tartronates, as well as anions containing fluoride, such as monofluorophosphates, hexafluoroaluminates, Hexafluorosi.likate, hexa-

209823/1 17 1 construction OP-K & ^

fluorostannate and fluorozirconate.

The insoluble salts are formed by a reaction between 1, G-di- (p-ehlorphonyl-biguanidoj-hexane as a free base or in the form of soluble salts, such as acetate, gluconate, or fluoride in v / as scr irrer reading with a salt or a weak acid of the desired / inions. This anion is necessary because of its later use irj dental cleaning agents, of course, in? ahnpflep; en ί | physiolo "must be safe and tolerable. The insoluble ones Fcerces can also be produced in situ if necessary, if a soluble form of compound with another ingredient of a Zahrspflep.c -neutels, such as, for example, NatriumnonoflucrophcsphHt or Ilat riurri-'i-lauroyl-sarcosinate, in reaction can kick.

For the monomeric and polymeric salts of the compound, the following formula are proposed: μ

T. Monomer -

Anion chlorhexidine anion

II. Polymer -,.

(... chlorhexidine anion chlorhexidine ...),

in which chlorhexidine is the cation of 1,6-di- (p-chloropheriyl-bi- {tuanido) -hexane and anion in formula I. a monovalent anion uni in formula II. a more variable; it means anion. In the polymer Salts siivi at least 2, but has 10 or more chlorhexidine cations available. 209823/1171

For use in dentifrices, the monomeric Disarcosinate and the polymeric monofluorophosphate preferred, because the disarcosinate in the presence of excess N-lauroylsarcosine odo.-r soluble salts of this compound in water dispersed and therefore easy to use in mouthwashes or toothpastes can be incorporated, and the monofluorophosphate Reason for the fact that it releases fluoride ions into the preparation. But you can also use the other insoluble salts good effect in tooth cleaning preparations such as toothpastes, toothpastes or translucent or transparent tooth gels be incorporated. In general, they are then present as discrete particles and can be in the gel or on the surface of the gel can be determined. They can also be non-translucent Creams with these compounds are mixed with the particles or streaks on the surface of the creams you can see. Insoluble compounds, such as d? .S Disarcosinate, which in the presence of excess M-lauroyl-sarcosine or its water-soluble salts can be dispersed, are preferably in mouthwashes or in toothpastes incorporated.

The insoluble compounds are the dentifrice in amounts of 0.01 to 5 wt.%, And preferably 0.05 to 1 wt. ", Based on the free base, is used.

The tooth cleaning agents according to the invention with a content of these water-insoluble salts usually have a pH-V. ^r ert zvri-

209823/1171

BATH

See 5 and 10 and preferably around 6 to 8. The pH value can be adjusted by a buffer system, for example citric acid, malic acid, tartaric acid and similar compounds can be used as buffers. Some of these compounds can then be reacted in situ with 1 ₃ 6-di- (p-chlorophenyl-biguanido} -hexane or a water soluble salt of this compound to form a water-insoluble polymeric salt react. At a pH value of above 10, the free base itself insoluble and then falls under the insoluble compounds to be used according to the invention.

The dentifrices generally contain a tooth-compatible and essentially water-insoluble polishing agent, as are generally known and used for toothpastes, chewable tablets, tooth powders and tooth gels. Examples of these compounds are dicalcium phosphate, tricalcium phosphate, insoluble sodium metaphosphate, aluminum hydroxide and hydrated aluminum oxides, colloidal silica gels, magnesium carbonate, calcium carbonate, calcium pyrophosphate, bentonite and mixtures thereof. The water-insoluble phosphates are preferably used as polishing agents, in particular water-insoluble sodium metaphosphate and / or calcium phosphates, such as dicalcium phosphate dihydrate. With very good effect and crystalline silica, up ^l younges 000 cm / g used v / ground with a particle size of up to 5 <m and a mean particle size of et v / a 1.1 / Uin and a Oesamtoberfläeho. The founding

209823/1171

BATH ORIGINAL

Toothpastes with insoluble salts of 1,6-di- (p-chlorophenyl-biguanido) -hexane and in particular with the insoluble disarcosinate are preferably also produced with a hydrated aluminum oxide from Alcoa as a polishing agent. "Alcoa C333" contains 64.9 wt.% Aluminum oxide, 0.008 wt.% Silica, 0.003 wt.% Ferric oxide, 0.25 wt. * Sodium oxide and at 10 ° C 0.37 3 wt moisture., Besides the particle size of the compound for all proportions is below 50 µm, with 84 % of the particles being smaller than 20 µm, and the specific gravity is 2.42. For the production of transparent tooth gels, colloidal silica gels such as '' Syloid 72 "and" Syloid 74 "," Santocel 100 "and alkali salts of complex aluminosilicates can be used as polishing agents, as these compounds have a refractive index similar to the refractive index of the gel matrix (from water and / or humectants and gelling agents).

However, the polishing agent itself, especially in the case of tooth powders, can also be the only carrier material. In general, the carriers contain additional ingredients, and the amount of the polishing agent is up to 95% by weight of the carrier. In toothpastes, the content of the polishing agent is neist to 20 to 75 ?, in Gew.i transparent tooth gels 5 to 50 wt.%, And in tooth powders or chewable to 95 G EVR. % of the carrier material. The most recently used aluminum silicate complexes have a Br-ech'Ui .-. Sin-iex of

2 0 9 8 2 3/1171 BAD ORIGINAL

about 1 M to 1.47, and contain up to 20 wt.% moisture, and sodium oxide to 10 Gew.5.

For the production of tooth powders, the various solid Ingredients in appropriate quantities and particle sizes mostly only mechanically mixed, such as grinding.

For the preparation of toothpastes and tooth gels, the amounts of liquid and solid ingredients are selected so that a eremite MASN-e obtained whose consistency squeezing from an aerosol container or a squeezable tube, v, for example, ie a Alurdniuin- or Pleitubo allowed · The The liquid component of these preparations usually contains water, glycerine, aqueous Sortitollösunpen, propylene glycol, StJiylenrlycol ^ 00 or mixtures thereof. Preferably a mixture of. V.'auser and a humectant such as glycerine or sorbitol are used. The total liquid content is around 20% by weight of the preparation. In clear dental gels where the refractive index is important, a mixture of 10 to 30% by weight of water, 0 to 80% by weight of glycerin and 20 to 80% by weight of sorbitol is preferred Gelling agents, such as methyl cellulose, hydroxyethyl cellulose, polyvinylpyrrolidone, starch or synthetic or inorganic, silicate-containing clays of the trademarks "Laponite CP" and "Laponite SP" in amounts of up to 10% by weight and preferably 0.2 to 5% by weight I made the mixture of Gesarritn.

209823/1171

BATH ORIGINAL

■ - 8 -

preferably used gelling agents are "Laponite CP" and "Laponite SP". Both compounds have the general formula [Si ₈ Mg _{5 # 0 # 1} Li ^ gO ^ Q used ₂₁ ^{0 '6} _N °' and ⁶ in quantities of 1 to 5 wt.%.

Furthermore, organic surfactants can be added to the preparations in order to have a better prophylactic effect uniform and thorough distribution of the preparations in the oral cavity and an improved cosmetic appearance reach. Anionic, nonionic, ampholytic or cationic surfactants can be used in the preparations Give net and foam properties. These include, for example, water-soluble salts of the essentially saturated higher aliphatic acylamides lower aliphatic aminocarboxylic acids with 12 to 16 carbon atoms in the Fatty acid, alkyl or acyl radical, such as N-lauroyl sarcosine or disodium, potassium or ethanolamine salts of N-lauroyl-sarcosine, N-myristoyl-sarcosine or N-palmitoyl-sarcosine. These compounds should be essentially free of soap or similar higher fatty acid compounds, since these negatively affect the effectiveness of the compounds, the use of the sarcosine compounds is particularly favorable, as they have a pronounced and prolonged hindrance to acid formation in the oral cavity due to carbohydrate breakdown and a certain reduction in the solubility of tooth enamel in acidic solutions cause. The salts used of the substituted

209823/1171

Biguanido-hexanes are used in a stoichiometric excess Any surfactants present are easily dispersed and can then be incorporated homogeneously into the tooth cleaning preparation.

The condensation products can be used as nonionic surfactants of sorbitan monostearate with about 60 moles of ethylene oxide, Condensation products of ethylene oxide with propylene oxide condensation products of ethylene glycol ("Pluronics") and as amphoteric surfactants can be used quaternized imidazole derivatives of the trademark "Miranol", such as "Miranol CoM" will.

The combination of insoluble ones containing fluoride anions Salts such as, for example, of the monofluorophosphate of 1,6-di (p-chlorophenyl-biguanido) -hexane and quaiternized imidazole surfactants is particularly desirable because it allows the formation of Brown stains on the tooth enamel are prevented very effectively, and furthermore these combinations do not have a bitter taste and have excellent antibacterial activity.

Surface-active germicides or bactericides can also be used cationic compounds are added to the preparations. Examples of these compounds are (Di-isobütylphenoxyäthoxyäthyl) -dimethyl-benzyl-ammonium chloride, Benzyl-dimethyl-stearyl-ammonium chloride, tertiary amines with a fatty alkyl group with 12 to C atoms and two oxyethylene groups on the nitrogen atom (with one

209823/1171

- ίο -

Content of 2 to 50 xthanoxy groups per molecule) and their Salts, compounds of the general formula

(CH ₀ CH ₀ O) H.

\ C. d. Z

in which R is a fatty alkyl group with 12 to 18 carbon atoms, and x, y and ζ are an integer of 3 or greater, sq ~ like their salts with mineral acids or organic acids. These compounds are preferably added in amounts of 0.05 to 5 wt.% Of the dentifrices according to the invention, the amount used in each case should be in stoichiometric excess over the amount used of l, 6-di- (p-chlorophenyl-biguanido) -hexane in the form of of the free base.

Furthermore, the dentifrice can contain various additives be added, such as dyes and whiteners, coloring agents, preservatives, silicones, chlorophyll compounds, Ammonia-containing compounds such as urea, diammonium phosphate or mixtures thereof and others Auxiliary materials. The amount of these auxiliaries added depends on the particular compound selected and may be the Do not adversely affect the properties of the dentifrice.

The insoluble, antibacterial salts result in the

209823/1171

Tooth cleaning products do not have an unpleasant or bitter taste. The taste can, however, be changed by adding various flavorings or sweeteners, such as by adding essential oils of spearmint, peppermint, Gaultheria, Sassafras, cloves, sage, eucalyptus, Marjoram, cinnamon, lemons or oranges or sodium methyl salicylate. Sucrose, lactose, can be used as sweeteners. Maltose, sorbitol, sodium cyclamate, perillartin or saccharin Find use. The total amount of flavors and sweeteners together is approximately 0.01 to 5% by weight or more of the Dentifrices.

A fluorine-containing compound can also be added to the tooth cleaning agents to achieve better prophylaxis and hygiene in the oral cavity, such as, for example, reducing the solubility of tooth enamel in acid and protecting against caries. Examples are sodium fluoride, tin-II-fluoride, potassium fluoride, potassium-tin-II-fluoride (SnP ₂ -KF), potassium fluorozirconate, sodium hexafluorostannate, tin-II-fluorofluoride and sodium monofluorophosphate. These compounds dissociate in or split off fluoride-containing ions and are used in effective but non-toxic amounts of mostly O ₄ I to 1% by weight , based on the content of water-soluble fluoride ions. Potassium hexafluorocirconate, sodium hexafluorostannate and sodium monofluorophosphate can be mixed with the free base of 1,6. Di- (p-chlorophenyl-biguanido) -hexane form insoluble polymeric salts in situ, while an excess of these compounds can be effective as a source of fluoride ions. Particularly preferred

209823/1171

Sodium fluoride, tin (II) fluoride and sodium monofluorophosphate are used as well as their mixtures.

In addition, other antiseptics can dentifrices are in amounts up to 5 wt.% Added. These compounds include, for example

N ¹ - (4-chlorobenzyl) -N ^ - (2,4-dichlorobenzyl) biguanide; p-chlorophenyl biguanide;

k -chlorobenzhydryl biguanide;

k -chlorobenzhydryl guanyl urea; NJ-lauroxypropyl-Nlp-p -chlorobenzyl biguanide;

l- (LauryIdimethylammonium) -8- (ρ-chlorobenzyl-dimethylammonium) octane dichloride;

5,6-dichloro-2-guanidino-benzimidazole; N -p-chlorophenyl-Ni-lauryl biguanide; 5-amino-1,3-bis (2-ethylhexyl) -5-methyl-hexahydropyrimidine; 1,6-ßis- (2-ethylhexylbiguanido) -hexane

and their non-toxic salts.

To improve gelling, to better thicken and to improve the transparency of the dentifrice, synthetic, finely divided silica gels, for example the trademarks "Cab-o-Sil M-5", "Syloid 2 * 1 * 1", "Syloid 266" or "Aerosil D-200" are added in amounts to 1 to 5 wt.%.

209823/1171

When producing toothpastes and especially tooth gels, an attempt is usually made to use as little air or gas as possible to be left in the preparation. The "Unimix" device, which can be found in "Process Engineering", is particularly suitable for venting September 11, 1970, pp. 81-85. this device contains a mixing device that can be turned clockwise or counter-clockwise and followed by a cockroach eater so that the surfaces of the device are always scraped clean. The scraping knife preferably consists of one Plastic such as polytetrafluoroethane, the. is compatible with the various components of the mixture. By the arrangement the mixing device and the scraper knife on a central raised column and by a hydraulically operated, va ~ kuur :: tight lid, very little air is incorporated during manufacture. First, mostly the gelling agent and a Part of the liquid mixture of water and / or humectant mixed in the device; the remaining liquid can then separately with the polishing agents and other components (except those to be added at the end, such as essential oils) mixed in the "Unimix" device and the two Mixtures are then mixed together in this device. If desired, the small amount of air contained in the preparation removed after applying a vacuum to the device. Processing of the ingredients can be done at room temperature or higher Temperatures are made. .

209 823/1171

. - in -

The following examples are intended to explain the invention in more detail. Unless otherwise stated, all parts and percentages relate to weight.

Example 1

A non-translucent toothpaste was made from the following ingredients;

Identificati hurry shares

Glycerine 20

Hydroxyethyl cellulose 1,2

hydrated alumina

(Alcoa C333) 52

Sodium N-lauroyl sarcosinate 2 1,6-di (p-chlorophenyl biguanido) hexane digluconate 0.886

Sodium saccharinate 0.2

Flavor (peppermint) 1

Water q.s. ad 100.0

During the production, the 1,6-di- (p-chlorophenyl-biguanida) -hexane-disarcosinate is used Formed in situ and evenly dispersed by the excess sodium N-lauroyl sarcosinate. at Using the toothpaste will reduce the number of bacteria in the oral cavity and decrease the buildup of plaque, whereby there is no staining of the tooth enamel and the toothpaste has a pleasant taste.

BATH 209823/1 171

Example 2

A non-translucent toothpaste was made from the following ingredients:

Components Shares glycerin 20th Hydroxyethyl cellulose 1.2 crystalline silica gel
(Minusil 5 / Um) 15th Miranol CpM 1

1,6-di- (p-chlorophenyl-biguanido) -hexane-monofluorophosphate 0.55

Sodium saccharinate 0.2

Flavors (spearmint) 1

Water q.s. ad 100.0

In the manufacture of this toothpaste, the 1,6-di- (p-chlorophenyl-biguanido) -hexane-monofluorophosphate is used in finished form, added together with the silica gel. Also this toothpaste reduced the number of bacteria in the oral cavity and reduces the build-up of plaque! with no staining on the enamel results. This toothpaste has a pleasant taste.

Example 3

A clear tooth gel was made from the following ingredients:

209823/1171

Components Shares

Sorbitol (70 ^) 50

Glycerine 25

"Laponite SP" 2

Sodium N-lauroyl sarcosinate 2

1,6-di- (p-chlorophenyl-biguanido) -hexane diacetate 0.619

IJa tr ium- sac char in at 0.1

Aerosil D 200 3

Sodium aluminosilicate 16

Flavor 1

Color 1

V / ater q.s. ad 100.0

During the production of this tooth gel, 1,6-di- (pchlorphenyl-biguanido) -hexane-disarcosinate is formed in situ and is caused by the excess sodium N-lauroyl sarcosinate dispersed. The transparency of the tooth gel is not impaired by the dispersed salt.

The sodium aluminosilicate used has a refractive index of 1.1 kg , a moisture content of about 6 %, an average particle size of about 35 / uni and, after sieving, a loose bulk density of about 0.07 g / cm / sq.

Example H

The following components were used to create a transparent,

209823/1 17 1

speckled toothpaste made:

Be_s t and parts
Sorbitol (70 % - ± z)
glycerin
Laponite SP
Miranol C ₃ M

1,6-di- (p-chlorophenyl-biguanido) -hexane-monofluorophosphate

Aerosil D 200

Sodium aluminosilicate Flavor

colour

VJasser

Ante ile 43 25

0.35

q.s. ad 100.0

During the production of this toothpaste, discrete particles of 1,6-di- (p-chlorophenyl-biguanido) -hexane-monofluorophosphate were used clearly visible in the clear toothpaste. That used Sodium aluminosilicate was the same as that used in Example 3.

Example 5

1,6-di- (p-chlorophenyl-biguanido) -hexane-monofluorophosphate became by mixing dilute stoichiometric solutions of 1,6-di-ip-chlorophenyl-biguanidoJ-hexane digluconate and sodium monofluorophosphate in water in the form of an almost white, oily precipitate of the water-insoluble 1,6-di- (p-chlorophenyl-biguanido) -hexane-monofluorophosphate with a melting interval of I83 -.

^209823/1171 BADOR ₁ G ₁ NAt

obtain.

Example 6

The production of ljo-Di-Cp-chlorophenyl-bi ^ uanicloJ-hexane citrate was done by mixing dilute solutions of Sodium citrate and 1,6-di- (p-chlorophenyl-biguanido) -hexane digluconate. The reaction product was obtained as an oil at room temperature, which slowly solidified to a sticky, solid mass.

209823/1171 ^copv

PAD CF '

Claims (1)

Claims 1. Zahnreinir.mittel containing 1,6-di- (p-chlorophenyl-biguanido) -hexane, characterized in that it is a water-insoluble salt of 1, G-di-Cp-chlorophenyl-biguai-iidoJ-hexane in Amounts of 0.01 to 5 wt. 3, based on the free base ₅ contains. 2. Tooth cleaning agent according to claim 1, characterized in that that the insoluble salt in monomeric form with monovalent Anions. 3. Tooth cleaning agent according to claim 1 and 2, characterized in that that the monomeric anion is a dihydrochloride, Dihydrop.enbromide, dihydrop; eniodide, disaccharate, Contains disarcosinate or dibenzoate. Ij. Tooth cleaning agent according to claim 3> characterized in that it contains a disarcosinate as the water-insoluble salt. 5 · number: ireinir; uni * uni means according to claim 4, characterized in that the disarcosinate is uniformly dispersed, and that the carrier is higher aliphatic sarcosines or their water-soluble salts with 12 to 10 carbon atoms in the aliphatic - 209823/1171 COPY BAD ORIGINAL see group in excess amount, based on the stoichiometric ratio of the free Bη, 00 of the l, 6-Oi- (p ~ chlorphen, yl-bir ^r , uaniclo) -hexane contains, 6. Tooth cleaning agent according to claim 5, characterized by ^ that there is sodium N-lauroyl sarcosinate in stoichiometric Contains excess. 7. Tooth cleaning agent according to claim 1, characterized in that that it is a water-insoluble polymeric salt with polyvalent anions. " 8. Zahnreinij ^ unfrsmittel according to claim 1, characterized in that the polyvalent ^ anion is a phosphate, citrate, malate, tartrate - or tartronate anion. 9. Tooth cleaning agent according to claim 7, characterized in that that the polyvalent anion is a fluorine-containing anion from the group of monofluorophosphate, hexafluoroaluminate, Hexafluorosilicates or hexafluorostannate Is flaorozirconate anions. 10. Zannrein solvent according to claim 9, characterized in that that it contains monofluorophosphate as a polyvalerite anion of the insoluble salt. 209823/1171 ^C0PY BATH ORIGINAL 11. Tooth cleaning agent according to claim 1 to 10, characterized characterized in that it is an essentially water-insoluble, Contains tooth-compatible polishing agent. 12. Tooth cleaning agent according to claim 11, characterized in that that it contains the insoluble salt in a carrier of gelling agent and a liquid of water, Contains humectants and / or mixtures thereof. 13 · Tooth cleaning agent according to claim 12, characterized in that that it is alr> gelling agent a synthetic, inorganic silicate clay of the formula 0.6 "0.6 ⁺ Ma contains. l4. Tooth cleaning agent according to claims 12 and 13, characterized in that that there are colloidal silica gels or alkali salts "of aluminosilicate complexes in one as a polishing agent Contains transparent carrier. 15 · Tooth cleaning agent according to claim 14, characterized in that that it is a sodium salt of an aluminosilicate complex as a polishing agent contains. l6. Zahnr-'inirunKsnittel according to claim 11 and 12, characterized in that that it is air hydrated, abrasive 209823/1171 copy ' BATH - 22 - Contains aluminum oxide. 17. Tooth cleaning agent according to claim l6, characterized in that that the 1,6-di- (p-chlorophenyl-biguanido) -hexane as disarcosinate in a carrier with a content a stoehiometric excess, based on the free base, of sodium N-lauroyl sarcosinate is present. Process for the preparation of the water-insoluble salts des l, 6-di (p-chloroph ^ nyl-biguanido) -hexane according to claim 1 to 17, characterized in that l, 6-di (p-chlorine- te s- phenyl-biguanido) -hexane as a free base or in the form of a soluble salt with a weak, polyvalent one Acid or its soluble salt, preferably in aqueous solution, is reacted. 19. The method according to claim 18, characterized in that the weak acid or its water-soluble salt is phosphoric acid, Citric acid, malic acid, tartaric acid or tartionic acid can be used. 20. The method according to claim l8, characterized in that a fluorine-containing anion from the group monofluorophosphate _5, hexafluoroaluminate, hexafluorosilicate, hexafluorostannate or fluoroairconate are used as the weak acid or its water-soluble salt. 209823/1171 21. The method according to claim 20, characterized in that conofluorophosphate is used as the polyvalent anion will. 209823/1171