DE2000851C3 - chewing gum - Google Patents

Description

The invention relates to chewing gum made from a chewing gum base and a dental care additive.

It is well known and proven that the development of yic acid as a result of the splitting of easily fermentable carbohydrates under the action of acid-forming oral bacteria one of the Main causes of dental caries is D -_- process or the mechanism of dental caries is essentially characterized by a decalcification of the inorganic tooth part and a decomposition of the organic matrix accompanied or followed. The acids build up on the tooth surface, and when they don't are neutralized or otherwise destroyed, demineralization of the tooth is quick.

So far, toothpastes and similar preparations have usually been used to clean teeth can be applied to the tooth surface, and certain suggestions for development have already been made Suggested by drug-based toothpastes that prevent tooth decay and increase tooth decay able to suppress. Many of them contain various inhibitors, such as fluorides or amides.

Dental chewing gum and lozenges based on acid-precipitated skimmed milk whey with additives such as tragacanth gum solution, essential oils and calcium or magnesium phosphates have been proposed in DE-AS 12 27 197. Chewing gum or gum-like masses with one Content of mechanically cleaning bodies of certain hardness and grain size, which are used to avoid the Acid formation, preferably containing synthetic sweeteners such as saccharin, are known from AT 1 76 636.

Another way to control tooth decay is to use sodium fluoride for systemic treatment To add effect to drinking water or to apply it locally to the tooth surfaces, and has also already found some recognition. Another way of checking dental caries is The use of antibiotics, such as penicillin, has proven to be somewhat beneficial in this regard proven, but on the other hand is not without certain disadvantages including sensitization of the patient, thereby diminishing its value as a caries control agent.

Despite these numerous proposed means of suppressing acid which is formed in the Oral cavity or its neutralization, the problem of combating dental caries seems much more complex and not simply by using the usual toothpaste preparations once or twice a day to be solvable by the consumer. Obviously, effective dental caries control requires that any bacterial growth inhibitor is effective for so long after it has been introduced into the oral cavity must remain that it can also offer protection against decomposition between the periods of use or even beyond. Conventional toothpastes offer not this protection and on top of that have the disadvantage that their active ingredients quickly leave the oral cavity be washed out, which shortens the contact time between the active ingredient and microorganisms will.

Thus, it is evident that there is still a lack of usable means and preparations to make up for this time the formation of oral microorganisms and acids between two introductions into the oral cavity fight.

Accordingly, the invention aims primarily to provide an anti-caries preparation in the form of Chewing gum that eliminates many of the disadvantages involved in the

jo use of the usual ones for combating dental caries Dentifrices occur.

Another goal of the invention is to create an anti-caries-active chewing gum that does not last long only formation or growth of oral microorganisms in the oral cavity, but also acid formation effectively can suppress and therefore not only during the chewing period, but also after throwing it away Protection granted.

Accordingly, in a chewing gum, the invention consists of a chewing gum base and a dentifrice Additive, the chewing gum being characterized by the fact that it acts as a caries-preventing additive

Pyruvic aldehyde, preferably 0.1 to 2.0%,
Glycolaldehyde, preferably 0.5 to 2.0%, and / or
⁴ ' glyceraldehyde, preferably 0.5 to 5.0%, or
Λ-hydroxypropionaldehyde, preferably 0.1 to 2.0%,

each based on the weight of the chewing gum. Particularly preferred are chewing gums that

V) based on their weight, 0.1 to 2.0% Pyruvic aldehyde and 0.5 to 2.0% glycolaldehyde, 0.1 to 2.0% pyruvic aldehyde and 0.5 to 5.0% Glyceraldehyde, or 0.5 to 2.0% glycolaldehyde and 03 to 5.0% glyceraldehyde, or 0.5% pyruvic aldehyde and 2.0% glyceraldehyde.

In the following, the invention is explained in more detail in various exemplary embodiments with reference to drawings explained.

The invention is based on the knowledge that this

M) extremely effective inhibitors against aldehydes Lactic acid formation (90% or higher) and growth of oral streptococci and bacilli are. this revealed extensive studies and tests carried out both in vitro and in vivo on certain

h) compounds, including in particular those mentioned Aldehydes which have also been found to be readily incorporated into chewing gum bases and turn them in during the chewing process

released to such an extent that they have the desired degree of activity for combating dental caries of 90% or more.

The F i g. 1 to 6 show in graphs the effect of chewing gum compositions with different contents of pyruvic aldehyde alone or together with glyceraldehyde on the growth of oral microorganisms and / or acid formation over different incubation times; of these shows

Figure 1 shows the effect of a flavored chewing gum base with pyruvic aldehyde (determined by direct chewing) on acid formation by a Mixed population of oral microorganisms; the titratable degree of acidity in ml is on the ordinate 0.050 η sodium hydroxide and the incubation time in hours plotted on the abscissa; Curve 1 corresponds to a sample without pyruvic aldehyde, curve 2 to a sample with 0.5% pyruvic aldehyde and curve 3 of one with 1.0% pyruvic aldehyde;

F i g. 2 the effect of such a chewing gum base with pyruvic aldehyde (determined by direct chewing) on the growth of a mixed population of oral microorganisms, whereby on the Ordinate the bacterial population on a logarithmic scale and the incubation time on the abscissa in Hours is applied; Curve 1 again corresponds to a sample without pyruvic aldehyde, curve 2 to one those with 03% pyruvic aldehyde and curve 3 one with 1.0% pyruvic aldehyde;

F i g. 3 the effect of a saliva extract from a flavored chewing gum base with 0.5% pyruvic aldehyde and 2.0% d, l-glyceraldehyde on acid formation by oral streptococci, whereby on the Ordinate of the titratable degree of acidity in ml of 0.050 η NaOH against the incubation time in hours on the Abscissa is plotted; the dashed curves relate to experiments with Streptococcus sp. GS-5 and the solid curves for Streptococcus sp. FA-I, the two upper curves with a Comparison gum extract without cariostatic substance and the two lower curves were obtained with a test kriostatic gum extract;

4 shows the effect of a saliva extract from a Gum base with 0.5% pyruvic aldehyde and 2.0% d, I-glyceraldehyde on the growth of oral StreptocOCci, with the bacterial population on the ordinate on a logarithmic scale versus the incubation time is plotted in hours on the abscissa; for the curves that applies to FIG. 3 said;

F i g. 5 the effect of a saliva extract from a gum base with 0.5% pyruvic aldehyde and 2.0% d, I-glyceraldehyde on acid formation by oral microorganisms; where is on the ordinate Titratable degree of acidity in ml of 0.050 η NaHO plotted against the incubation time in hours on the abscissa; the dashed curves were mi; oral mixed inoculum, the solid curves with Lactobacillus casei, the two upper curves (see brackets) with a comparison gum extract without cariostatic substance, the lower curves obtained with a test cariostatic gum extract; and

F i g. 6 the effect of a saliva extract from a gum base with 0.5% pyruvic aldehyde and 2.0% d,

ι »I-glyceraldehyde on the growth of oral microorganisms; on the ordinate is the bacterial composition on a logarithmic scale against the Incubation time in hours plotted on the abscissa; the assignment of the curves corresponds to that of Fig. 5.

The above-mentioned inhibiting effect occurs when - as already stated - the chewing gum mass 0.1 to 2% Pyruvic aldehyde, 0.5 to 5% glyceraldehyde, 0.5 to 2% glycolaldehyde, or 0.1 to 2% α-hydroxypropionaldehyde Furthermore, s '.:' i showed that mixtures of pyruvic aldehyde or glyceraldehyde with Glycolaldehyde in the specified concentrations - based on the individual effects - only an additive Overall effect, on the other hand those made from pyruvic aide

2> hyd and clyceraldehyde apparently a by about 10% increased, i.e. synergistic overall effect.

Glycolaldehyde and glyceraldehyde are readily available as commodities of this degree of purity

jo available that they are added to foodstuffs can. The exploitation of the invention can, however, be subject to legal restrictions, in particular through the Food Act, are subject.

Pyruvette aldehyde falls as an aqueous distillate or

j5 aqueous phase of an azeotropic concentrate is almost colorless and then contains about 20 to 60% practically pure compound in addition to less than 0.04% Formaldehyde. The latter can be eliminated by further purification down to less than 0.02 percent by weight will.

The evaluation of the aforementioned aldehyde compounds anti-caries activity has occurred through numerous studies and tests both in vitro and simulated as well as actually in vivo. The results of these tests are given in Tables I to VIII below compiled and then both for yourself and, as far as possible, on the basis of the graphs discussed in more detail.

In the table columns »Basic approach« are also the

components already mentioned, such as "gum base", "adhesive substance" and the like, too other common chewing gum ingredients such as corn syrup, sugar, corn sugar, flavorings and the like, listed as they are normally used in the preparation of chewing gum masses.

Table I.

Effect of saliva extracts from pyroclastic aldehyde test gum on oral microbe mixtures ^a )

Try chewing gum

The basic approach to pyrites
aldehyde")

Extraction process

Chewing time
(min)

Degree of inhibition ^c )
Acid formation growth

Rubber base,

Abhesivsutitanz,

Flavor

Seduce extract ^d ) 60.0

direct chewing ^e ) 2.5

lorlsct / imi!

Try chewing gum

Bren / grape- (irundansat / alUehyd ^h )

Rubber base.

Abhesive sublance.

Flavor

Rubber base,

Adhesive substance,

Fruit juice flavor

üummibasis, Abiiäsivsubsian / .. 1% taste stimulus

Extraction tubes Kiiuilaucr (min) Fxtraktverfahren '') 60.0 direct chewing 2.5 Fxtraktverfahren ¹ ') 60.0 direct kaucs 2.5 Extract method ¹¹ ) 60.0 UIICMC> IMIUCII 2.5 direct chewing 5.0

Inhibition degree ¹ ) Acid growth

4 + 4

+ 4 t

The results given apply to an oral mixed inoculum in human saliva after incubation for 24 hours

at 37 C in the presence of chewing gum extract. ^h ) Substance purified from manufactured product using diethyl acetate. ^c ) Pie symbols indicate the following degrees of inhibition:

for acid formation inhibition (%)

0-

+ - 10-

+ 25-

+ + 75-

+ + + 90-

+ + + + 99-100

for growth inhibition (%)

0 75

+ 75 - S9

+ 90-98

+ + 99 - 99.89

++ 99.9-99.989

+ + + + 99.99

') The sample flasks contained 50% saliva, part of which came from the saliva extract of the test chewing gum.

The final concentration of carbohydrates (glucose / sucrose) was 8% and the theoretical active ingredient content was about 0.1%. ^e ) The test flasks for the direct chewing tests contained 1 part of chewing gum saliva expectorant per 1 part of carbohydrate-free base. The final concentration of carbohydrates in the flask was on average 7.7% for the 2.5-minute and 6.9%

for the minute chewing time.

Table II

Pyrographic aldehyde in test gum extracts obtained by direct chewing, on mixed oral microorganisms ^a )

Try chewing gum

Pyrane basic approach aldehyde-inhibiting effect ^c ) with regard to acid formation, chewing duration maximum efect

Incubation Degree 24-hour EfTeki duration Degree (min) (Hours.) 2.5 10 +++ 5.0 11th + + - 2.5 16 ++++ +++ 5.0 10 + + + 2.5 2.4 +++ +++ 5.0 10 + + - 2.5 24 +++ +++ 5.0 6th +++ + 2.5 8th +++ + 5.0 8th +++ + 2.5 8th +++ + 5.0 6th +++ - 2.5 10 ++++ + 5.0 6th ++++ - 2.5 8th +++ ₊ 5.0 8th +++ I.

0.5 1.0 1.5 2.0 1.0 1.0 1.0 1.0

Chewing gum base chewing gum base chewing gum base chewing gum base

flavored chewing gum base, adhesive substance

Chewing gum base adhesive substance

flavored chewing gum base, adhesive substance

Fruit juice flavor chewing gum base, adhesive substance

20 00 85

Table II (continued)

Try chewing gum Basic approach / Chewing time llemniclTckl ¹ ) regarding growth Bravely grapes Maximum tect aldchyd ^h ) Incunation wheel 24 hours (min) permanent effect ( ⁰ A) Chewing gum base 2.5 (SId.) ^Degree 0.5 5.0 6 ++ Chewing gum base 2.5 6 ++ 1.0 5.0 16 ++++ + - Chewing gum base 2.5 10 ++++ 1.5 5.0 12 + +++ ++ Chewing gum base c 2.5 6 ++++ 2.0 5.0 24 ++++ ++++ flavored chewing gum base 2.5 fi +++ 1.0 5.0 6 ++ Chewing gum base 2.5 3 ++ 1.0 Adhesive substance without taste 5.0 3 ++ flavored chewing gum base, 2.5 3 + 1.0 Adhesive substance 5.0 10 ++ Fruit juice flavored chewing gum 2.5 7 -L-L-
J T — Γ - 1.0 base material, adhesive substance 5.0 3 ++ 6 ++

^a ) The results listed apply to an oral mixed inoculum in human saliva. The sample flasks each contained 1 part of chewing gum saliva expectorant and sterile human saliva to 2 parts of matrix. The final concentration * n carbohydrates (glucose / sucrose in the contents of the flask was about 3.9% for the 2.5-minute and 3.7% for the 5-minute chewing time. Incubation took place at 37 C.

^b ) Synthesized from dihydroxyacetone.

^c ) See Explanation of symbols Pur table I.

Table JII

Effect of glyceraldehyde in test gum saliva extracts obtained by direct chewing on mixed oral microorganisms ¹¹ )

Try chewing gum Basic approach Basic approach Chewing time Inhibiting effect ^c ) with regard to acid formation Glycerine
alriehvri (min) Maximum effect
ntkuöaiiuns- gray 24-5ui.-ni7eki
duration degree (%) Chewing gum base 2.5
5.00 (Hours.) 1.5 Chewing gum base Chewing gum base 2.5
5.0 6 ++
6 + + - 2.0 Chewing gum base Chewing gum base 2.5
5.0 6 +++ +
11 +++ + 3.0 Chewing gum base 2.5
5.0 10 +++ ++
10 +++ + 5.0 Table III (continued) 24 +++ +++
24 +++ +++ Trial chewing gum i Glycerine Chewing time growth aldehyde Maximum effect (%) (min) Incubation degree 24 hour efiect
duration degree 1.5 2.5
5.0 (Hours.) 2.0 5.0 3 + -
no - - 6 ++ + -
9 ++++ +

10

continuation

Experimental chewing gum Kaudiiucr growth Ulcerin
iildehyd Basic / (min) Maximum effect
Incubation
clauer (%) 2.5
5.0 (Hours.) 3.0 Chewing gum base 2.5
5.0 9
6th 5.0 Chewing gum base 24
24

Degree

24-Sld.-KITect
Degree

+ + f l

The results listed apply to an oral mixed inoculum in human saliva. The sample flasks contained I part each of chewing gum-saliva expectorant and sterile human saliva aul'2 parts of basic mass. The final concentration of carbohydrates (glucose / sucrose) in the flask contents was about 3.9% for the 2.5 minute and 3.7% for the 5 minute

^h ) See explanation of symbols for door, table I.

Table IV

Effect of glykoaldehyde ¹ in test gum saliva extracts on mixed oral microorganisms ³ )

Try chewing gum Basic approach procedure Chewing time
(min) Degree of inhibition Glycoaldehyde ^b ) Chewing gum base Extract process
Direct chewing 60.0
5.0 Acid growth
education 1.0 impure Chewing gum base Extract process
Direct chewing
Direct chewing 60.0
2.5
5.0 ₊₊ ... 1.0 cleaned Chewing gum base Extract process
Direct chewing
Direct chewing 60.0
2.5
5.0 ++ ++++ I. 2.0 cleaned Xt ₊ tttt

^a ) The results listed apply to an oral mixed inoculation material in human saliva after incubation for 24 hours

at 37 C.
") See explanation of symbols for table I.

Table V

Effect of pyruvic aldehyde in combination with glyceraldehyde in test gum extracts obtained by direct chewing on mixed oral microorganisms ^a )

Try chewing gum Basic approach Chewing time Inhibiting effect ^b ) regarding Acid formation Pyrography glycerine Maximum effect aldehyde aldehyde Incubation Degree 24-hour efTect (min) duration Degree (%) (%) (Hours.)

0.5 *) 0.5 chewing gum base

0.5 °) L ₁ O chewing gum base

0.5 *) 1.5 gum base

0.5 ^c ) 2.0 gum base

0.5 ^d ) 2.0 gum base

Adhesive substance

Il

Table V (continued)

ersuchs chewing gum (%) Basic approach. Kauz.eil Inhibitory effect ^b ) on growth Bren / Grape Glycerine
rildehyd aldehyde 0.5 (min) Maximum effect
Degree of Incubation, 24hr Effect
duration degree (%) 1.0 Chewing gum base 2.5
5.0 (Hours.) O, 5 ^C ) 1.5 Chewing gum base 2.5
5.0 3 ++
3 + 0.5 ') 2.0 Chewing gum base 2.5
5.0 10 ++ +
6 +++ Π 0.5 ^c ) 2.0 Chewing gum base 2.5
Sf) ΙΟ ++ + -
10 +++ 0.5 ^c ) V (continued) Chewing gum base
Adhesive substance 2.5
5.0 3 ++ +
12 ++ 0.5 ^d ) 10 ++++ + +
6 ++ Tabel

Trial chewing gum pyruvine glycerine

Basic approach

Chewing time

Clamping effect ^b ) with regard to acid formation, maximum effect

UlUbIlJU UlUWl IJF U Flavor (min) Incubation Degree 24-hour eriekt Chewing gum base 2.5 duration Degree (%) (%) Adhesive substance 5.0 (Hours.) 0.5 ^d ) 2.0 Chewing gum base 24 + + + + + + Adhesive substance 2.5 9 ++ + + + Fruit juice flavor 5.0 0.5 ^d ) 2.0 Chewing gum base 2.5 8th + + + + + 5.0 6th + + + + 0.5 ^d ) 2.0 24 ++ + + + + 9 ++ + +

Adhesive substance

Table V (continued)

Try chewing gum aldehyde Basic approach Chewing time HemmefTekt ^b ) regarding growth Pyruvine glycerine Maximum effect rldehyd (%) Incubation Degree 24-mercenary effect 2.0 (min) duration Degree (%) flavored 2.5 (Hours.) 0.5 ^d ) Chewing gum base 5.0 10 ++ ₊ 2.0 Adhesive substance 6 +++ - Chewing gum base 2.5 0.5 ") 2.0 Adhesive substance 5.0 10 ++++ ++ + Fruit juice flavor 2.5 5 ++ + 0.5 ") Chewing gum base 5.0 10 +++ + 3 ++ +

Adhesive substance

^a ) The results listed apply to an oral Mlsch inoculum in human saliva. The sample flasks each contained 1 part chewing gum saliva expectorant and 1 part sterile human saliva per 2 parts matrix. The final concentration of carbohydrates (glucose / sucrose) in the contents of the flask was about 3.9% for the 2.5-minute and 3.7% for the 5-minute chew. The incubation took place at 37.degree.

^b ) See explanation of symbols for table I.

^c ) Substance purified from manufactured product using diethyl acetate.

^d ) Synthesized from dihydroxyacetone

13 14

Table VI

Effect of the rate of release of potential cariostatic active ingredients from test chewing gum obtained by direct chewing on the inhibition of oral microorganisms ³ )

Try chewing gum Conc
tration Conc
tration Basic approach 5 minutes
Chewing time
Intervals ¹¹ ) Inhibiting effect ^c ) with regard to acid formation Active ingredient (%) (%) (min) Maximum effect
Incubation degree 24-hour effect
duration degree 1.0 1.0 Flavoring
Adhesive substance
customary 1.2.5
2.2.5 (Hours.) Pyrography
aldehyde 1.0 1.0 Flavoring
Adhesive substance
customary 1.2.5
2.2.5 11 ++++ +++
7 +++ Pyrography
aldehyde 0.5
2.0 0.5
2.0 Flavor
Adhesive substance
customary 1.2.5
2.2.5 7 +++ Pyrography
aldehyde
d, l-glycerin-
aldehyde Table VI (continued) 12 +++ ++ - Ι
ό +++ + - Try chewing gum Active ingredient Basic approach 5 minutes
Chewing time
Intervals ¹¹ ) HemmefTekt ^c ) regarding growth (min) Maximum effect
Incubation grade 24 sld. Effect
duration degree Peg
aldehyde Flavor
Adhesive substance
customary 1.2.5
2.2.5 (Hours.) Pyrography
aldehyde Flavor
Adhesive substance
customary 1.2.5
2.2.5 11 +++ +++
7 ++ - Pyrography
aldehyde
d, l-glycerin-
aldehyde Flavor
Adhesive substance
customary 1.2.5
2.2.5 7 ++ - 22 ++++ +++ - Ι
ό ++++

*) The mixed results apply to chewing gum saliva extracts compared to an oral mixed inoculation material. The sample flasks contained 1 part of chewing gum saliva speculum to 1 part base. The final concentration of carbohydrates (glucose / sucrose) in the flask contents was 7.9% for the first and 2.2% for the second chewing interval of 2.5 minutes each.

^b ) The same piece of kai gum was chewed for 5 minutes and the saliva and gum extracts formed during the first 2.5 minutes chewing time were collected separately from the extract formed during the second 2.5 minutes chewing time and examined.

^c ) See explanation of symbols for table I.

Furthermore, the inhibitory effect of pyruvaldehyde / d.l-glyceraldehyde combination ions on acid formation in a range of broth tube concentrations of various microorganisms, namely Streptococcus sp. PA-I, Lactobacillus casei and oral mixed microorganisms, identified which led to excellent results,

Table VII

Summary of the in vivo evaluation of pyruvic aldehyde, glyceraldehyde and glycolaldehyde carried out according to the usual evaluation ^{method 9)}

Active ingredient Experimental number of Tribe and animal Caries yield average 21.7 Calculated duration animals Occurrence extent Tooth decay back average 8.6 64.8 crowd ¹ ') (Days) Pyruvic aldehyde 90 8th Osborne-Mendel 23.3 + + + Strain 1, rats Comparison (diet ")) 7th Osborne-Mendel Strain 1, rats

Kiirlset.'ung

Active ingredient

Test number of strains and animal duration animals

(Days)

Caries bulge

miltl. average

Occurrence extent

Calculated

Caries back

urgency ^h )

Pyruvic aldehyde
Comparison (diet ^c ))

90

Glyceraldehyde 56 Comparison (diet ^e )) Glyceraldehyde, 91 crystalline dimer Comparison (diet =)) Glycolaldehyde 90 Comparison (diet ^d )) Glycolaldehyde 90 Comparison (diet ^c ))

20 20

8 8 8

8th
20th

20 20

Osborne-Mendel strain 2, rats Osborne-Mendel strain 2, rats

Albino, hamster

Osborne-Mendel strain 2, rats

Osborne-Mendel tribe !, rats

Osborne-Mendel strain 2, rats 5.95
15.08

8.0
27.5
15.0

23.5
5.53

12.85
5.44

13.94

14.55 38.80

21.8 80.9 29.4

51.0 13.19

35.45 11.69

35.38

^a ) The agents were added to the diet in an amount of I%.

^b ) The symbols indicate the following approximate extent of the caries suppression: ++ = 50%; +++ = 75%.

^c ) Evaluated by student tests with a 95% degree of reliability.

^d ) Commercially available cariogenic rat diet, main ingredients: ground rice and whole milk powder. ^c ) Commercial diet, main ingredients: powdered sugar and skimmed milk powder.

Table VIII

Comparison of the in vitro activity of cariostatic compounds and related ones Structures against oral microorganisms

link formula description Activity ") be plus acid empirically structurally dimeric glycol aldehyde educational Pyruvic aldehyde inhibition (C ₂ H ₄ O ₂ I ₂ (HIGH ₂ CHO) ₂ Propionaldehyde ++++ C ₃ H ₄ O ₂ CH ₃ COCHO «■ -hydroxypropionaldehyde ++++ C ₃ H ₆ O CH ₃ CH ₂ CHO jS-hydroxypropionaldehyde + C ₃ H ₆ O ₂ CH ₃ CHOCHO Glyceraldehyde +++ C ₃ H ₆ O ₂ HIGH ₂ CH ₂ CHO + - C ₃ H ₆ O ₃ HIGH ₂ CHOHCHo ++++

*) See note ^c ) in table I.

In the simulated in vivo methods, microbiological samples of the extracts were obtained by direct mi Chewing the chewing gum as well as obtained from saliva extracts of the gum. The majority of these Gums were made from common, commercially available gums with common gum base and Flavor additives made. For others, similar> The influence of an adhesive substance was also investigated in recent studies (Detackifier) and the flavor component on the potential cariostatic activity of the compounds investigated, each test chewing gum with a comparison gum from the same basic approach. but was compared without the active ingredient.

The above gum base consists of the nutrient-free, chewable chewing gum substance, as set out in the United States Food, Drug, and Cosmetics Act. In which the Food Additives Amendment Ordinance on Chewing Gum Ingredients (Federal Register, p 4419, May 9, 1962) describes paragraph (al the for

Chewing gum base compositions permissible ingredients and paragraph (c) defines the term "chewing gum base" as "fully or partially fabricated, nutrient availability, chewable substance selected from one or more of this Art'iKels designated ^r> in paragraph (a) and defined components «. Usable chewing gum bases which can be used with advantage for the production of the chewing gum compositions according to the invention are described, for example, in US Patents 2284804 and 21 37 746.

The flavors used in the experiments consisted mainly of common flavors and some also from fruit juice aroma. Ii

If used, the adhesive consisted of a water-soluble, hydrolyzable tannin in a water-based, hydrophilic gel. A typical such agent, that of a given matrix added, contains water, glycerine, gelatin and tannic acid.

Such adhesive substances are used in the chewing gum compositions described below to reduce the tendency of the Chewing gum for sticking to teeth and in particular to counteract certain types of teeth and artificial teeth. A hydrophilic gel, e.g. B. in the preferred embodiments gelatin, becomes one with water heavy paste processes and forms with a water-soluble, hydrolyzable tannin, such as tannic acid, an adduct bonded via hydrogen bonds, whereby the last-; ·; less water soluble and slower can be extracted from the rubber. The plasticizer in the form of glycerine serves as a co-solvent and at the same time increases the gel viscosity compared to only aqueous approach. r>

In addition to the plasticized gelatin-tannic acid adduct, the adhesive substance can preferably also still contain some free tannic acid which causes the initial non-stickiness after hydration of the gum is prevented from being extracted too quickly by the gel.

In this context it should be noted that the American patent 32 55 018 a variety of Abhesive subslances, including the softened gelatin-tannic acid adduct and method preferred here describes how to incorporate them into chewing gum. The use of this preferred substance but of course does not exclude that the chewing gum compositions according to the invention also any other type of Abhesive substance and in particular all in the aforementioned patent specification with regard to composition, Manufacture and incorporation may contain the substances described.

The anti-caries agent, ie aldehyde, is brought in the same manner as the Abhäsivsubstanz or y, flavoring agent and optionally one as a premix with them into the rubber.

In the simulated in vivo tests tabulated above, the cariostatic potential of the batches was studied microbiologically and in special cases _b Q chemically-analytically. The chewing gum extracts were prepared by human persons chewing gum directly and examined for antimicrobial activity in such a way that the effect of the extracted cariostatic substance μ on the one hand on acid formation and on the other hand at the same time on the growth of the microorganism mixture of the mouth, which together with Saliva, sucrose and other substances leached from the chewing gum were removed from the oral cavity, the influence of the duration of contact between the two also being taken into account. These organisms were therefore the normal inhabitants of the oral cavity, originating from the oral mucosa, tongue and teeth, along with some piping-associated organisms, which were detached from the tooth surfaces when chewed by gum composed according to the invention or aroma-free, sugar-free and plasticized by paraffin.

The special mixer for chewing gum examinations was used as a mechanical device for extracting of soluble substances from large amounts of chewing gum, iLh. Approaches from 150 to 175 g, using sterile uses human saliva. Aliquots of aseptic extracts prepared in this way were added to their antimicrobial effect on pure cultures of Lactobacillus casei. Streptococcus spec. FA-I and Streptococcus spec. GS-5 (a human caries isolate) as well as against an oral microbe mixed fauna

The antimicrobial and anti-acid properties of chewing gum compounds Pyruvic aldehyde are given in Tables I and II. From them you can see that pyruvine aldehyde For example, in a 1 percent by weight concentration in the chewing gum, the formation of acid over a period of 24 hours by more than 90% and oral microbe growth by more over 16 to 17 hours of incubation time than 99.0%. In addition, the graphs in FIG. 1 and 2 the influence of Aldehyde concentration on these two effects during the experimental periods.

Further experiments were then carried out with 1 part each of chewing gum saliva expectorant and sterile saliva Carried out on two parts of basic mass, with the oral microbes as the only source of carbon and energy only the glucose-sucrose mixture withdrawn from the gum during chewing was available. the Carbohydrate concentration in the sample flask was after dilution of the gum extract to one Quarter on average 3.9% for a 2.5-minute and 3.7% for a 5-minute chewing time. The results one can see these extensive direct attempts with chewing gum containing pyruvine aldehyde from Table II. in which the inhibitory effect at the time of incubation of maximum effect and at End of trial, d. H. after 24 hours.

Table III provides information on the antimicrobial effectiveness of glyceraldehyde alone in chewing gum. Thereafter, 3% glycerine aldehyde is required to have a convincing inhibitory effect on both oral microbe growth as well as acidification, and 5% of it results in both cases an almost complete inhibition.

From Table IV it can be seen that while the antimicrobial properties of glycolaldehyde are those of Inferior to pyruvic aldehyde, but significantly better than that of glycerine aldehyde.

Following the investigation of these three aldehydes alone, mixtures of pyruvic aldehyde and glyceraldehyde were also found in various concentrations, namely those of 0.5 percent by weight of the former and about 0.5 to 2.0 percent by weight of the the latter examined and explained in terms of results in Table V. From it one sees that the highest antimicrobial activity achieved with rubber seals

is, the 0.5 percent by weight pyruvic aldehyde and 2.0 percent by weight glyceraldehyde, so 2.5 Containing weight percent total aldehyde, and then about that of a gum mass of 1.5 Corresponds to percent by weight of pyroclastic aldehyde, regardless of whether this base material is only used as such or present together with an adhesive substance or a flavoring additive

Since the direct chewing method used acted on the mixture of microorganisms normally present in the mouth, it was not possible to use it to investigate the effect of this combination of active ingredients on a single type of bacteria. Therefore, a saliva extract was prepared under aseptic conditions in a special mixer from a gum made of base material, adhesive substance, flavoring as well as 0.5 percent by weight pyroclastic aldehyde and 2.0 percent by weight dJ-glyceraldehyde and with a correspondingly prepared comparison saliva extract from a commercially available, i.e. compared chewing gum not containing cariostatic agents. The composition contained in the test flask was adjusted so that it contained as much gum extract substance as possible as is obtained with direct chewing for 5 minutes, and the test conditions were the same as for the direct chewing tests reported in Table V. The results can be seen from the graphs in FIGS. 3 to 6. 3 and 4 show the influence on two types of oral streptococci including the strain GS-5 as a microorganism involved in human caries, namely an almost complete suppression of acid formation and a drastic suppression of the streptococcal cell fauna. FIG. 5 relates to a human mouth isolate, the Lactobacillus casei (ATCC 4646), and r, FIG. 6 to a mixed oralinoculate collected by different people.

Another investigation, reported in terms of results in Table VI, looked at how quickly the cariostatic active ingredient is released from the test chewing gum when chewed directly. Were compared two types of chewing gum, namely e: ne with only 1.0 percent by weight pyruvic aldehyde and one others with a combination of 0.5 percent by weight pyruvic aldehyde and 2.0 percent by weight glyce-4-, rinaldehyde. The gum was chewed for a total of 5 minutes, with that during the first 2.5 minutes The salivary and gum euract formed during the chewing period was also separate from that during the second 2.5 minute chewing period was collected and examined extract formed. Apparently they were in the first chewing period the main part of both the carious active substance and the carbohydrates, namely 78% of the total extractable released from the rubber. Even so, it was still a considerable one Inhibitory activity of the extract obtained during the second chewing period during the first 6 to 7 hours Observe incubation period. Long-term, d. H. 24 hour inhibitory effects were not measured.

In addition, in vitro experiments were carried out with combinations of pyruvic aldehyde, glyceraldehyde and glycolaldehyde, each of which was tested for its ability to reduce the acid produced by a pure culture of either Lactobacillus casei or Streptococcus spec. FA-I . At the same time b5 each active ingredient was examined individually. Further experiments on the inhibitory effect on acid formation showed that the aldehydes can be exchanged for one another in order to achieve an additive effect, but, as already mentioned, the combination of pyruvic aldehyde-glyceraldehyde produced a synergistic, ie greater inhibitory effect on acid formation than the only additive effect of the two aldehydes at the unused concentrations.

Table VII summarizes the in vivo evaluations of pyruvic aldehyde, glyceraldehyde and glycolaldehyde together. The results are based on standard laboratory technology, i. H. each test animal received For several weeks the aldehyde was added to his feed in 1 percent by weight. In all cases a decrease in caries of more than 50% could be observed. According to Table VII all of the aldehydes tested show a significant reduction in both incidence and extent of dental caries in laboratory animals.

In addition to these three aldehydes mentioned, α-hydroxypropionaldehyde, ß-l ^; Hydroxypropionaldehyde and propionaldehyde each in G, feiger concentration by means of a bouillon tube test for activity and percentage inhibition of acid formation by Lactobacillus casei and Streptococcus spec. FA-I examined.

Table VIII provides information on the results of these and similar comparative tests with pyruvic aldehyde, glyceraldehyde and glycolaldehyde. While these last three aldehydes resulted in a 99 to 100% suppression of the acid formation, -hydroxypropionaldehyde only achieved a 90 to 98% strength, and propionaldehyde and β- hydroxypropionaldehyde were much less effective. «-Hydroxypropionaldehyde can therefore also be regarded as an important anti-caries agent. This compound is effective in the concentration range of 0.1 to 2.0 percent by weight with 0.5 percent by weight being the preferred amount. It can be synthesized in usable purity by known processes. ^ -Hydroxypropionaldehyd as well as propionaldehyde are only moderate acid inhibitors and therefore less important as a chewing additive.

As already mentioned, the effective concentration of pyruvic aldehyde is 0.1 to 2.0% of the chewing gum mass weight and the preferred concentration above 0.5% thereof.

In the case of glyceraldehyde, the effective concentration range is 0.5 to 5.0 percent by weight of the chewing gum composition and the preferred concentration when used alone as a cariostatic agent is above about 2.0 Weight percent of it.

Glycolaldehyde is in amounts from 0.5 to 2.0 percent by weight, and preferably above about 1.0 Properly cariostatically effective.

The following examples illustrate the addition of the anticaries agents according to the invention to three different ones Chewing gum principles.

Examples 1 (A) to 1 (Z) relate to the production of normal chewing gum with respect to substance and Amount of varying composition including cariostatic agent according to the invention, example 2 refers to coated chewing gum and example 3 to balloon- '> the bubble gum. Obviously, the various chewing gum recipes are only examples of the addition of an anti-caries agent any chewing gum composition directed invention and can within the scope of protection in for the A person skilled in the art can be modified.

(Λ) (U) - 20 00 85 (I)) 1.0 - 1 (1·!) (Γ) - 22nd (G) - 1.6 - (II) - (!) - (J) - 21 20.0 20.0 - 20.0 1.0 20.0 21.0 - 21.0 - 21.0 - 20.46 - 19.82 - 2.6 2.6 - H c i s ρ i e I I 2.6 2.6 - - - 3.0 - 2.36 _ 2.28 20.1 20.0 20.0 20.0 15.7 2.0 14.2 - 11.2 5.0 12.98 11.74 55.2 55.2 (C) 53.7 53.7 57.1 - 57.1 57.1 - 60.45 62.08 1.6 1.6 20.0 1.6 1.6 1.6 1.6 1.6 1.55 1.49 Composition (parts by weight) 0.1 0.1 2.6 0.1 0.1 0.10 0.10 component 1.6 1.6 20.0 1.6 1.6 1.6 1.6 0.15 0.23 Gum base c 0.6 0.6 53.7 0.6 0.6 0.55 0.88 Gelatin-tannic acid adduct 0.9 1.0 1.6 - 0.5 I, (K) 1.00 Corn syrup - 0.1 - sugar - 1.6 0.5 Corn sugar - 0.6 - Tannic acid 0.5 Glycerin - Flavor 2.0 Pyruvic aldehyde - Glycolaldehyde Glycaldehyde (7-1 hydropropionaldehyde

Example I (continued)

Composition (parts by weight)

component (K) (L) - (M) (N) - 1.6 - 1.0 - (O) - 1.6 - (P) - - (U) - 1.6 - 1.5 (R) - 1.6 - Gum base c 19.05 20.37 - 19.86 20.8 - - 20.6 - 20.9 1.6 0.5 20.6 - 20.4 2.0 Gelatin-tannic acid adduct 2.20 2.35 - 2.28 - - 2.0 - - - - - - Corn syrup 13.24 12.92 11.77 18.5 18.3 - 18.6 - 18.3 - 18.2 - sugar 61.86 60.17 62.19 56.5 55.9 - 56.6 - 55.8 55.4 - Corn sugar 1.44 1.54 1.49 1.6 1.6 1.6 1.6 1.6 Tannic acid 0.10 0.10 0.10 Glycerin - 0.15 0.23 Flavor 0.71 1.00 0.88 Pyruvic aldehyde 1.00 1.00 0.50 Ulycolaldehyde - - Glyceraldehyde - 0.50 σ-hydroxypropionaldehyde - -

Example I (continued)

Composition (parts by weight)

component (S) - (T) - (U) (V) (W) (X) (Y) (Z) Gum base 20.5 20.4 20.2 20.7 20.5 20.57 20.46 20.0 Gelatin-tannic acid adduct - - - - - 2 ^ 7 2.36 2.6 Corn syrup 18.3 18.2 18.0 18.4 18.3 13.05 12.98 20.0 sugar 55.8 55.3 55.1 56.2 55.7 60.80 64.50 55.2 Corn sugar 1.6 1.6 1.5 1.6 1.6 1.56 145 1.6 Tannic acid - - - - - 0.10 0.10 0.1 Glycerin 1.6 1.6 1.5 1.6 1.6 0.15 0.15 1.6 Flavor - - - - - - 0.55 0.6 Pyruvic aldehyde 0.5 0.5 0.5 0.5 - 1.00 1.00 - Glycolaldehyde - - - - - - - - Glyceraldehyde 1.0 1.5 2.0 0.5 - - - £ 7-hydroxypropionaldehyde - - - - _ _

Example I.
(Continuation)

The gum base batch was softened by kneading in a maintained at 50 ⁰ C hot-mixer and then thoroughly mixed with the gelatin-tannic acid adduct. Then, one after the other, first all the corn syrup plus the anti-caries agent, then two thirds of the sugar-corn-sugar mixture, after thorough incorporation of the glycerine and the rest of the sugar-corn-sugar mixture were added. As the latter, the tannic acid and the flavor were added, and everything was worked through again well. Finally, the batch was discharged, cooled slightly and shaped and notched into sheets in the usual way.

Example 2

This example gives a general recipe for pinp coated chewing gum. The anti-caries agents are those given in Example 1. They can be made from pyruvic aldehyde in concentrations of 0.1 to 2.0 percent by weight, from glyceraldehyde in concentrations of 0.5 to 5.0 percent by weight, from glycolaldehyde in concentrations of 0.5 to 2.0 percent by weight or according to Example I from any combination of these substances within of the concentration ranges mentioned exist. But one can also use -hydroxypropionaldehyde in concentrations use from 0.1 to 2.0 percent by weight.

core Weight percent Glycerin 0.76 sugar 50.43 Corn syrup 2053 Corn sugar 1.90 Flavor 0.76 Rubber base 25.22 coating Carnauba wax 0.0! sugar 92.49 Gum arabic 5.52 Dextrin 138 Flavor 0.60

The core approach was based on the example
described manner mixed together and could also contain an adhesive substance of the type specified. Complete or partial addition of the anti-caries agent to the core was carried out according to the method according to Example 1.

After the core mass had been shaped into bars and cooled, it was cut into pieces and cut into weighed amount placed in a pan. A solution was made for the coating Sugar, syrup and gum arabic prepared. The pan was turned and started Each core piece was "poured over" from the syrup-gum arabic mixture and worked through it Warm air was dried on. During this pulling process was carried out at appropriate time intervals Flavor added alone or together with the anti-caries agent, if this is in the coating should be included. For the second coating, only sirap was used with no added gum arabic A total of forty coatings were applied and finally the finished pieces were made with carnauba wax polished

Example 3

This example relates to the formulation of a balloon or bubble gum mass with contained therein Anticaries active ingredient selected according to Example I and 2 and incorporated in the manner described earlier can be. The basic approach given can contain pyruvic aldehyde in a concentration of 0.1 to 2.0 percent by weight, glyceraldehyde in a concentration of 0.5 to 5.0 percent by weight and glycolaldehyde in a concentration of 0.5 to 2.0 percent by weight, these aldehydes again as in the earlier examples either individually or in any combination within those mentioned Concentration ranges can be used. You can also use Λ-hydroxypropionaldehyde in Add concentrations of 0.1 to 2.0 percent by weight.

Components

Weight percent

Rubber base

Corn syrup

sugar

water

Glycerin

Flavor

16.8

22.4

59.7

0.3

0.3

0.5

The gum base was softened by kneading in a hot mixer kept at 50 ° C. After that, all of the corn syrup along with the anti-caries active ingredient and still two thirds of the amount of sugar were good mixed in. Then water, glycerin, remaining sugar and finally flavor were added in sequence. Everything was thorough again worked through, and finally the batch was discharged, cooled slightly, and closed in the usual way Individual pieces of the desired shape and size shaped and notched.

From the above description of the compositions according to the invention with reference to preferred exemplary embodiments it is clear to those skilled in the art that these compositions can be used without departing from the spirit and the scope of the invention can be modified to a large extent. In this context It should be noted that ketoaldehydes and α-hydroxyaldehydes are apart from their antimicrobial properties if desired also directly and practically as a humectant in the preparation of the invention Chewing gum masses can be used because they meet the moisture requirements of the chewing gum .Tii production have a beneficial effect on the sugars and resins used. How this is done is not exactly known; in any case, pyruvic aldehyde Glyceraldehyde and glycolaldehyde and their mixtures are beneficial to the chewing gum complex affect when the mass remains moist and pliable. Thus, the compounds listed above provide in addition to their cariostatic effectiveness, the additional advantage that they are based on the invention Chewing gum compounds have a moisturizing effect.

In summary, the invention thus creates novel chewing gum compositions with cariostatic properties, which consists of a chewing gum base and one or more compounds in the form of There are pyruvic aldehyde, glyceraldehyde and / or glycolaldehyde or α-hydroxypropionaldehyde and possibly and particularly preferably contain adhesive substances and flavorings.

909 683/57

For this purpose 3 sheets of drawings

Claims (4)

Patent claims: 1. Chewing gum made from a chewing gum base and a dental care additive, thereby characterized in that it is pyruvic, glycolic and / or glyceraldehyde or Λ-hydropropionaldehyde contains. 2. chewing gum according to claim 1, characterized in that it, in each case based on weight of chewing gum, 0.1 to 2.0% pyruvic aldehyde, 03 to 2.0% glycolaldehyde, 0.5 to 5.0% glyceraldehyde or 0.1 to 2.0% Λ-hydroxypropionaldehyde contains. 3. Chewing gum according to claim 1, characterized in that it, in each case based on weight of chewing gum, 0.1 to 2.0% pyruvic aldehyde and 0.5 to 2.0% glycolaldehyde, 0.1 to 2.0% Brent grape aldehyde and 0.5 to 5.0% glyceraldehyde or O ^ to 2.0% glycolaldehyde and 0.5 to 5.0% Glycerinaldefeyd contains 4. chewing gum according to claim 3, characterized in that it, in each case based on the weight of the chewing gum, 0.5% pyruvic aldehyde and 2.0% glyceraldehyde