DE1617926A1 - Oral care products - Google Patents

Description

Applicant: UffTL ä7ER 1Γ.Υ. "Muee mnpar k 1, Rotterdam" Holland. Oral care products

The present invention relates to oral care products, i.e., "Means for caring for the oral cavity" It has been known for many years to make dentifrices containing germicides. «Germicides are generally used in dentifrices to improve the health of the mouth» been that microorganisms in the oral cavity a certain role in the development of dental caries, periodontal disease, abnormal breath odor and tartar deposits play "the regular use of a germicidal agent that is able to reduce the bacterial population in the mouth much, so 1st desirable ,,

However, one is at the introduction of an effective germicidal agent Into the oral cavity in such a way that the bacteria

riWnpopulation in the mouth for longer periods under control

109816/1944

encountered certain problems On the one hand, the concentrations of germicidal agent used cannot be seen2 * be high ". because high concentrations have an adverse effect which have normal tissues in the mouth and can also exert toxic effects «, The lower concentrations of germicidal Means «which can be used without hesitation in mouthwashes and toothpastes are able to produce satisfactory results Providing initial germ killing does not result in effective activity beyond a relatively short period of time.

The present invention provides a novel composition for reducing the bacterial population in the oral cavity o Not so much to try to destroy all or substantially all of the bacterial population in a single massive treatment, a particulate carrier for the germicidal agent is employed which comes to lie on the plaque of the tooth surfaces as well as in cracks and crevices, ζ "B _r between the teeth» The germicidal agent is adsorbed on the surface of the carrier * The carrier with adsorbed germicidal agent is hereinafter referred to as the Gtermlcid carrier- The term "complex" refers to the germicidal agent adsorbed on the surface of the carrier is sufficiently loosely bound "to be released from the carrier and to exert germicidal activity in the areas immediately adjacent to the carrier particle." At the same time, however, the germicidal agent is bound sufficiently tightly to be held in situ by the carrier to become so that it kills germs will exert hands effect for an extended period _o

Germicide-carrier complexes for use in the oral care products according to the invention can be prepared by precipitation methods. For example, the germicidal agent to be used is dissolved in a suitable solvent. Because the germicidal agent should be essentially insoluble in water, _see below which is dealt used in the preparation of the germicide-support complex solvents nor "malerweiee an organic solvent, such as, _e B _o is an alcohol, to be _o After preparation of the solution of the germicide with". means of the carrier of the solution is zugesetet * the carrier should be insoluble in the solvent used _a In order to deposit the germicidal agent on the surface of the carrier ", a non-solvent for the germicidal agent is added, which causes it to precipitate out of the solution because the germicidal agent is essentially insoluble in water _f What · * »Ser generally used for this purpose * after the precipitation of the germicidal agent in the presence of a carrier whereby a germieid-carrier complex is formed _r the solution is filtered to recover the complex * which, if desired, can be washed and / or dried.

(Xermicid-carrier complexes produced in this way can be used when putting together toothpastesj toothpowder and mouthwashes be used. In mouthwashes, depending on the type of the vehicle employed, a suitable suspending agent needed to suspend the carrier serraieid particles to support and prevent caking during storage «In toothpastes and tooth powders Carrier an ingredient specially designed for this purpose

109816/1944

or he can use the abrasive component of the dentifrice to be.

The germicidal agent used in the present invention can any of those conventionally used for oral hygiene purposes. Among the salient properties one of such germicides is that they are applied in the ■ The highest concentrations are physiologically acceptable and harmless, i.e. non-irritating, especially with regard to the mucous membranes with which they come into contact. The germicidal agent should also be essentially insoluble in water and have a melting temperature above body temperature, so that it remains adsorbed on the surface of the carrier particles within the oral environment is said to be substantially insoluble in water, and some low solubility is likely to be an attribute of an effective germicidal agent, "In the case of a dentifrice It is also important that the germicidal agent is essentially insoluble in the vehicle used in the dentifrice. In the case of mouthwash seeds, the vehicle is essentially aqueous, while in toothpastes a glycerine-water or a sorbitol-water mixture is the typical vehicle.

Typical, physiologically acceptable germicides which can be used in the practice of the invention include hexachlorophene, the habgenated salicylanilides such as tribromosalicylanilide, the halogenated carbanilides and a number of germicides of an antibiotic character, notably tyrothricin.

109816 / 19A4

The carrier used according to the invention can in general be any non-to3cigchea? 5 inert solid which Wasser-unlcSslish is una in the oral environment does not melt * The Particles of the 'carrier material © preferably have an average particle size in the range from 1 to 50 microns " A rope size range of 5 to 15 microns becomes special preferred"

Substances suitable as stock include, for example, thermoplastic resins such as powdered polyolefins (aJ, polyethylene and polypropylene powder) g powdered polystyrene ₉ powdered polyacrylic acid resins, powdered polyesters and powdered polyamide resins o. Thermosetting substances can also be used? Melamine = ^ epoxy and phenol ~ formaldehyde ~ resins are typical examples of this o As a carrier and also the abrasives _? which are suitable for use in toothpastes and tooth powdersp useful, such as "3 _a the various calcium phosphates ₉ silicon _{dioxides p} calcium silicate and alpha-aluminum oxide trihydrate"

Another Katogerie useful carrier particles are fibrous materials, "you can natural origin be ₉ such _a B _e soy""protein fiber ₉ or synthetic origin ^ as _ζ β Β β the fas '' ring nylons * polyester and polyolefins * The fiber diameter should in generally range from 1 to 50 microns. Fibrous carriers have the advantage that they can easily find their way into crevices and cracks in order to keep the germicidal agent in situ

109816/1944

In forming the germicide-carrier complex by the precipitation method described above, the solvent for the germicidal agent should of course be one in which the carrier material is essentially insoluble. Typical, usable in the present invention germicides are the lower aliphatic alcohols, for "B _a ethyl alcohol and isopropyl alcohol soluble. Accordingly, resinous substances which are significantly soluble in these same alcohols should be avoided ". It is also desirable that the carrier be compatible with other ingredients that may be present in the dentifrice. eg certain forms of calcium phosphates, which may be incompatible with any fluorides present. It is evident that these factors can be controlled to a considerable extent by the selection of solvents and vehicle systems which have the necessary properties for each component of the dentifrice.

Resins such as the polyolefins and thermosetting resins as well as the inorganic abrasives such as the various Claciumphoephate, Siliciumdioiyd and Silicates, as well as the protein fibers are particularly preferred because of their substantial insolubility in the usual organic solvents used for Solution of the germicidal agent are very useful.

The amount of weight of the wearer used in relation to the

109816/1944

Mb » ξ fcÄ *,

Weight of the germicidal agent is preferably at least about 5: 1 and i usually t substantially planer _t Since "preferred to keimtötencten of carrier EengenvarhältrJ.e: Central · by a number of factors * eg the potency dea germicide dominated .. products can have composition adjusted to high potency * therapeutic. ¹ applications under fold! '. be restricted "_; In the products, a composition adjusted to a lower potency for sale as toothpastes or mouthwashes can be used for unsupervised use. Composition issues _o If used too much support "for example, can be _0" in a mouthwash, the product obtained Shoo? ·> Willingness among consumers · miss In the case of toothpastes and tooth powders, it may be desirable to have a high ratio carrier · apply germicide ₉ by nan diw dental abrasive is used as the backing _c to thereby reduce the number of necessary fabrication steps ",

Microscopic examination of by the precipitation method described above shows germicide-carrier complexes produced Crystallized germicidal agent attached to the surface of individual particles of the carrier material * The solution of the germicidal agent used in the preparation of the complex are essentially not in good condition? to dissolve the material of the carrier particles or to penetrate into it in some other way. The * precipitation method does not lead to germicides, the bind really loosened within the backing material.

BAD ORKBiHAL 10301 G / IS ^

When incorporating the germicide-carrier complex in oral care products the proven approach expertise is applied · The germicide-carrier complex is added in an amount "sufficient to provide an effective amount of germicidal agent" in the Liquid agents such as mouthwashes are usually added as suspending and dispersing agents used to the liquid vehicle

Typical approaches fall within the following general ones Limits:

Mouthwash

Germicide carrier complex 0.5 # - 10 i »

Suspending agent (vegetable gum) 0.1 $> - 0 _e 9 $> dispersing agent 0.1 # - 2 $

Flavorings, solubilizers

for this and water rest

Tooth powder

Grinding wheel 5 ρ - 95 "ß>

Foamer 0.1 ^ - 1 i »

Thickener 0 i »'- ~ 1 #

Flavors <. "---

Germieid carrier complex ^x ' 5 f ° - 95 i »

^x 'The backing can form all or part of the grinding wheel. " If a non-abrasive carrier is used, the germicide-carrier complex will normally make up about 5 1 ° - 50 % of " the base"

Toothpaste

Grinding wheel 10 i * ~ 50 fo

Foamer 0 _f i % - 3 %

Flavorings

Body building agent O $ = 20 ύ

Vegetable gum 0 # - 3 %

Germicide-carrier complex ^x ^ 5 -f> «= 50 #

Vehicle ^xx ^ remainder

10 9 816/1944

# β>, ι Λβ aao

The backing can make up all or part of the abrasive grit. * If a non-abrasive backing is used, the germicide-backing complex usually makes up about $ 5> ~ $ 30> of the toothpaste «- ·

'' The vehicle is usually a glycerine-water or a sorbitol-water mixture *

The amount of complex used in each sollfee Palle ausreioheng lim from about O ₅₁ to about Ol # 2 ^ germicide to deliver * "Obviously, it requires a recognition, in which a large proportion is used by carrier ₉ of a high ratio support: germicide Medium »If a small amount of carrier is used, the ratio of carrier to germicidal agent is lower _o .

The present invention will now be illustrated by the following examples are _o

Example 1 .

A hexa-chlorophene-polyethylene complex was made as follows manufactured!

25 g of a polyethylene powder with an average particle size of 10 microns was added to 500 % denatured ethyl alcohol ", 1 $> Hexachlorophene (based on the alcohol weight) was added and the mixture was stirred for 10 minutes",

Then three times the volume of distilled water was added and the suspension was stirred for 30 minutes, with sioh the hexachlorophene would precipitate on the polyethylene particles The mixture was filtered through a Buchner funnel and

109816/1944

the complex was washed three times with distilled water.,

/ Δ-aqueous emulsion with the above Hexachlorophsn Polyethylene Kompiex © into 5 prepares When disas emulsion was 60 seconds long used as a mouthwash, was at the Ztiim- plaque detectable after 6 hours of germicidal activity © au watch *

The deposited onto the polyethylene amount of germicide made 60 $> the starting material aüSo The rest of the germicide remained in the water Alkohoi "I <ösimg and could be retrieved for later use * In Gerniicid-carrier complex, the weight ratio Trägei was · s Germicid about 8.3 ϊ 1 »

Example 2 ι

According to the procedure described in Example 1, a series of similar complexes was prepared "where the alcoholic solution of the germicidal agent was of varying concentration" namely fluctuated in the range between about 0.25 '$> and 1 i => and gave complexes in which the Weight ratio of carrier % germicidal agent was in the range from about 8 s 1 to about 35: 1 "The germicidal activity of the complex obtained was evaluated on normal agar plates inoculated with test organisms." After inoculation, a sample of the hexachlorophene-polyethylene complex is applied bringing the agar and the plate is incubated at 37 ⁰ G for 24 to 48 hours = germicidal activity is calibrated by a transparent zone or ISS · hibierungszone _# known that the sample of Hexachlorophen-

109816/1944

Polyethylene complex surrounds and in what growth the test « Organisms Prevented «The following results have been made receivedϊ

gabeile I

Inhibition of digestion complexes Complex area in mm

Polyethylene / 1 / ° hexachlorophene ** 20

"/ 0.75 / o ⁿ 20

«/ 0.50 ■% ^M. 20th

' ^lf / 0 * 25 ■% " 20

^x 'The concentration data relate to the amount of hexachlorophene in the solution from which it was precipitated »

The above experiments show that the activity of the hexachlorophenes can be maintained? while reducing its concentration in the solution from which it is precipitated, _o

Similar results are obtained using powdered polypropylene instead of the powdered polyethylene, as in the example 1 is listed, began "

Example 3 '

From dicalcium phosphate with an average particle size of 2-4 Kikrons and hexachlorophene, according to the in Example 1 described procedure, under Ersat «of the polyethylene a complex produced by dicalcium phosphate *. The weight ratio of carrier to germicidal agent in the obtained Complex was on the order of 8 s "U - the germicidal one Activity of the complex was determined with the following results checked:

109816/1944

- 12. ': "■" Table II

Inhibition zone of test complexes Test complex: ^x zone e in mm

Polyethylene / O g 25 1 " hexachlorophene 20 dicalcium phosphate / 0 ^ 25 ί ° hexachlorophene 17

^x 'In the preparation of these complexes, hexachlorophene was _{precipitated from an O 4} , 25 days alcoholic solution _o

Example J.

Example 1 was repeated again, but with spun Soy protein fiber with a fiber diameter of 30-50 microns instead of the polyethylene mentioned in Example 1 was used * The order of magnitude of the weight ratio carrier: germicidal agent in the complex obtained was 8: 1. When the complex was tested for germicidal activity, a Inhibition zone of 20 mm found «

Example 5

Using a 1 _? 0% alcoholic solution of hexachlorophene, an amount of a hexachlorophene-polyethylene complex was prepared according to Example 1. After the precipitation operation, the complex formed was filtered off _s washed three times with distilled water and dried «

A 5% suspension of the hexachlorophene-polyethene complex was prepared and the usual plate tests for hexachlorophene "activity" were carried out on the slurry, comparing the activity of the liquid phase of the slurry with the activities standardized Hex: achlcn? o ^: phen solutions, it was found that the liquid phase of the

109816/1944

visualization Since ₀ O ₈ 06 fo contained hexachlorophene _o

Mouthwash was made for further tests, * ifudem man. a 5 A-ig® aqueous suspension of the HösachJ-orophen-polyethylene complex in a 0 _v , 1 show solution of hydroxyethyl cellulose suspended and this combination treated in a colloid mill ", a relatively stable suspension was obtained Tested by test subjects in vivo to determine whether the hexaehlorophene-polyethylene complex was noun in relation to tooth plaque and whether the mouthwash can be used to reduce the level of bacteria in the mouth ₀ as indicated by bacterial counts in saliva? to maintain *

The members of the test groups rinsed her mouth for 1 minute with a 5 $ ~ aqueous slurry of HexachlD ~ rophen-PolyäthylenrKomplexeso samples of dental plaque _o then obtained at time intervals by scraping both interproximal surfaces of the lower front teeth, the samples were dissolved in sterile GKLasphiolen given »

These samples were mixed thoroughly using a sterile platinum needle and placed on agar seeded with an oral micrococeus sensitive to hexachlorophene * The presence of hexachlorophene was indicated by a clear inhibition tone _? which immediately surrounded the plaque sample ^{after incubation at 37 °} C. for 24 to 48 hours,

The following results were obtained:

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"14" = ■,
Table III

Group members with plaque showing inhibition agon e

Start !, Immediately 2 hours 4 hours 6 "hours

Sample after · afterwards afterwards afterwards before mouth a / lündwas «·
laundry serge «?

First test group

(4 personnel) 04 3 2 2

Second test group

(4 people) 0 4 2 2 1 Third test group

(4 people! 0 2 1 - O

Because the sampling method works at random "a test group of 4 participants will not always provide plaque samples * which activity demonstrate in each case" An explanation can be * that the sampled material was deposited near the mouthwash _p The fact that activity at least in which a barren other of Gruppenmitglisder is found, '* is considered highly significant "This Teet has been carried out by hexachlorophene many times using mouthwashes on dsr basis and it was this place earlier ,, that plaque samples showed no inhibition zones ο ■ ·,

With the help of another person, total numerical values were recorded on ben plates, with the bacterial Population (organisms per cc) in saliva before and after application The use of the test mouthwash was estimated. The following results were obtained?

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PlatteB total number table values

Early in front of Mtmdwäsefoe 16,110 * 000

15 minutes after Mw.Edwash 1 »639 * 000

2 1/2 hours after ^ft 8 _e ? 50 «000

5 1/2 ^fr "' ⁵ 3-44O0OOO'

The above results show that the particles of the Hexachlorophene-Polyäthylexi-Koinplexes in the mouthwash on the dental plaque and several hours in the cracks and cracks in the mouth remained slightly after application and significantly reduced the bacterial population in the mouth for extended periods of time «

Example β

It became another amount of a hexahedral-polyethylene complex produced * whereby the hexachlorophene was precipitated from its 1 yo alcoholic solution onto the polyethylene o The complex obtained was turned into a toothpaste incorporated in the following composition s

_ Anhydrous calaiim phosphate

Hexachlorophene-polyethylene complex ³ ^

Polyethylene

Granulated silica Carboxymethyl cellulose water

Sorbitol solution (70 · />) - Aroma paste and foaming agent

^ The concentration of germicidal agent «based on the total batch, was 0 _? 15 fa _v

A commercial Dical.'iiiimphosphat Kreiae ^ toothpaste ^ to which O ₅ , 15 1 ° hexachlorophene was added served as a control.

£ * O ORIGINAL 109816/1944

10, 00 15th , 00 15th , 00 0 • 25 35 , 00 22nd , 05 Best

Test groups used one or the other toothpaste for two percent long, and during this period the subjects brushed their teeth according to their normal habit *, none. ^{f% of} people used a different measure of oral hygiene after regular use of the toothpaste in question for this period of time, PIaque samples were placed on seeded agar plates * using an organism sensitive to hexachlorophene * and the plates were then kept at 57 for 24 to 48 hours ⁰ G incubated. The following results were obtained:

Table Y

Number of test persons whose plaque showed recognizable hexachlorophene activity (test groups of 5 members each)

Trial toothpaste control 2 0

109816 / 194A

Claims (1)

Munich, November 29, 1967 P / J Patent claims - TIa ii ι m ii ι Wn ami MTH Tn Ii IWi-HIi I mm 1 * Oral care product containing particles of a water-insoluble material, characterized in that an essentially water-insoluble germicidal agent is adsorbed on the particles. 2ο oral care product according to claim 1, characterized in " that the water-insoluble material is a thermoplastic resin 3 »Oral care product according to claim 2, characterized _? that the thermoplastic resin is a polyolefin » 4 ^ oral care product according to claim 3, characterized in that that the polyolefin is polyethylene or polypropylene, Oral care product according to claim I _9, characterized in that it is in the form of a toothpaste or tooth powder containing an abrasive, and that the water-insoluble material represents the abrasive or a part thereof. 6 »Sundpflegemittel according to any one of the preceding claims" characterized in that it O ₉ S to 95 wt _o # particles having adsorbed thereon germicidal agent comprises ". 7, oral care product according to one of the preceding claims, 109816/1944 At characterized in that the ratio of the weight of the water-insoluble material to the weight of the germicide the mean is at least 5: 1., 8, oral care product according to one of the preceding claims, characterized _? that hexachlorophene is the germicidal agent ", 9 «Oral care product according to one of the preceding claims, characterized in that the germicidal agent from 0.01 to 2 wt _. # of the oral hygiene product " 1Oo oral care product according to one of the preceding claims, characterized in that the germicidal agent adsorbs to the particles of the water-insoluble material thereby is that the particles with a solution of the germicidal agent in a solvent ,, which by the water-insoluble material cannot be absorbed and in which the hater-insoluble material is insoluble, brought into contact and germicidal agent out of the Solution has precipitated, with precipitated germicidal agent has been adsorbed on the particles " 11o particles of a water-insoluble carrier material, characterized in that essentially water-insoluble germicidal agent is adsorbed thereon, the ratio of the weight of the particles of the carrier material to the weight of the germicidal agent being at least 5: 1 _o 12 »Particles according to claim 11, characterized * that they 109816/1944 an average size of 1 to 50 microns own*. 13ο Participation according to claim 11 or 12 _? sprouted thereby _? . that the carrier material is a thermoplastic Harss " Ho particles according to claim 1 or 12 »characterized« in that the carrier material is an abrasive tooth care product isto 15 »Particles according to one of claims 11 to H» thereby marked? that they have been obtained by mar? Particles of the carrier material with a solution of the germicidal agent in a solvent which is from Carrier material cannot be absorbed and in which the carrier material is insoluble »brought into contact and the germicidal agent precipitated out of the solution has, with precipitated germicidal agent to the wearer = material particle has been adsorbed *, ■ 109816/1944