Note: Descriptions are shown in the official language in which they were submitted.
3~
This invention relates to the production of
comestibles. More specifically it is concerned with a candy
product which is rendered anticariogenic through the use of a
novel cariostatic additive.
The prior art has long sought a means to compensate
for the cariogenic potential of comestibles, particularly
foods containing high preponderances of sweeteners such as
sucrose and other sugars. It has been theorized that, when
sugars are placed in the mouth, they give rise to the
production of acids which promote dental caries.
A contributing cause of dental caries in children is
the adherence of highly refined sugars and their decomposition
products to the dental plaque after ingestion, coupled with
the slow rate of oral clearance, or the ability to produce
high amounts of acid, or combinations of such factors.
A number of cariostatic agents have been evaluated
in the past in systems wherein the agent is applied or
consumed topically (i.e. directly on the teeth) in the form
of a dentifrice (e.g., a toothpaste or a toothpowder). However,
knowledge gained on the effectiveness of eariostatic agents
used in sueh topieal applieations has not permitted predietion
of efficacy for these eariostatie agents in other applieations,
sueh as in foods, and partieularly in foods eontaining a
substantial portion of sugars.
Unfortunately, known eariostatie agents have in
general not provided any substantial degree of protection when
used in foodstuffs. Thus, known eariostatic agents sueh as
fluorides,
~ 2 -
3~
I phosphates, vitamin ~, nitro~urlns, ammonium compo~nds, iodoacetic
2I acid and the like, when added separately to a food stuff containing
31 a high percentage of sugar, have little direct topical effect in a
4 1 foodstuff environment.
For the foregoing and other reasons, dental researchers
6 have continued their efforts to develop new anticariogenic agents
7 which not only demonstrate a high level of anticariogenic effec-
81 tiveness but which are non-toxic, stable, and widely available. It
gI has been suggested that aluminum salts may have a beneficial effect
o¦ in reducing dental caries or in facilitating the uptake of fluoride
11¦ by the dental enamel. See, e.g., Manly et al., "Substances Capable
12 of Decreasing the Acid Solubility of Tooth Enamel", J. Dent Res.
151 28: 160 (1948); Regolati, et al., "Effects of Aluminum and Fluo-
14 ride on Caries, Fluorine Content and Dissolution of Rat Molars",
15 1 Hel. Odon. Acta. 13: 59 (1969); and Kelada, "Electrochemical
16l Characteristics of Free and Complexed Fluorides in Drinking Water
17 l¦ and The Effects of Aluminum and Iron on Fluoride Incorporation Into
Tooth Enamel," Univ. Michigan Thesis (1972).
lg ! In vitro studies have shown that pretreatment of enamel
with aluminum solutions resulted in increased fluoride uptake when
21 followed by treatment with a fluoride solution; however, treatment
22 with combinations of aluminum and fluoride did not afford any added
23 benefit over that of fluoride alone. McCann, "the Effect of Fluo-
24 ride Complex Formation on Fluoride Uptake and Retention in Human
Enamel", Archs. Oral Biol. 14:521 (1969); and Gerhardt, et al.,
26 "Fluoride Uptake in Natural Tooth Surfaces Pretreated with Aluminum
27 Nitrate", J. Dent. Res. 51:870 (1972). Moreover, the foregoing
28¦ techniques have dealt primarily with the use of aluminum in combi-
29 ! nation with fluorides and have not focussed on the effect of alumi-
30I num in the absence of fluoride.
31~I
32 1 -3-
!!
l l ¦
63~6
1 It has heretof~re ~een s~ggested that ~he addition of a
2 ¦source of aluminum to the diet may reduce the cariogenic potential
3 ~thereof. However, studies have to date suggested that aluminum is
4 ¦ ineffective as a dietary anticariogenic agent. Thus, Van Reen, et
5 ¦al., "Trace Elements and Dental Carries: Molybdenum, Aluminum, and
6 ¦Titanium", Helv. Odont. Acta., 11:53-59 (1967), concluded (p. 57)
7 ¦ that "Aluminum potassium sulfate when added to the drinking water
81 of rats to provide 10, 50, or 100 ppm of aluminum did not afford
9¦ any protection against dental caries. . . ." The same conclusion
o¦ was reached with aluminum added to the dietrary ration fed rats, as
11¦ reported by Wynn et al., "Dental Caries in the Albino Rat on High
12¦ Sucrose Diets Containing Different Amounts of Aluminum", J. Nutri-
1~ tion, 54:285-290 (1954), and with parenterally injected aluminum,
14 1 as reported by Kruger, "The Effect of "Trace Elements" on Experi-
15 ¦I mental Dental Caries in the Albino Rat", Univ. of Queensland Papers,
161 1:1-28 (1959).
17 Nor has the use of aluminum salts in dentrifices demon-
1~ strated a desirable result. Thus, while French Patent No. 3610M
19 describes a specific combination of aluminum lactate, aluminum
20 fluoride and calcium pyrophosphate, the abrasive interferes with
21 ¦ the aluminum by reacting therewith to form insoluble aluminum
22 ¦ phosphate. Similarly, U.S. Patent 3,095,356 uses aluminum salts
23 I such as aluminum fluoride to coact with insoluble sodium metaphos-
24 phate abrasives to reduce the solubility of such abrasives and to
25 increase fluoride uptake, but without independent therapeutic
26 advantage being taken of the aluminum.
27 U. S . Patent No. 3,282,792 describes low pH stannous
28 fluoride dentifrices stabilized against precipitation and oxidation
29 of stannous tin ions through the use of hydroxyl substituted di-and
30 ¦ tri-carboxylic acids. However, nothing is said in the patent
31 11
S2 ,1
lll -4-
~L~9~i3~6
l egardirlg the use of aluminum Wlth respect to systems thnt do not
2 contain fluoride. Similarly, while U.S. Patent 3,937,806 teaches
3 ¦oral compositions comprising indium and fluoride to which malic
4 ¦acid is added to stablize the indium, the patent does not recognize
S ¦that beneficial results may be achieved with aluminum and carbo-
6 ¦xylic acids without incorporating fluoride.
7 I Canadian Patent No. 928,272 describes acidic dentifrices
8 ¦comprising a combination of surface active substances and albumen
9 ¦coagulating substances such as certain carboxylic acid salts of
10¦ aluminum and other metals. However, this patent likewise fails to
1¦ teach that significant dental health benefits can be achieved with
12 ¦ aluminum containing comestibles.
15¦ Thus, while some elements are known to inhibit dental
14¦ caries (e.g., F, Mo, Sr, and V) and while others are known to
15¦ promote caries (e.g., Se, Mg, and Cd), the preponderance of data on
16 ¦ aluminum indicates that it is dental caries inert as classified by
171 Navia, "Effect of Minerals on Dental Caries", in Dietary Chemicals
1~¦ v. Dental Caries, A.C.S., Washington, D.C. (1970).
19¦ U.S. Patent 3,772,431 concerns a mouthwash tablet contain-
ing a effervescent couple (e.g., a solid basic material and a solid
21 lorganic acid such as fumaric, citric, tartaric), which produce CO2
22 ¦when dissolved in water, in combination with an astringent-desensitiz-
23 ¦ing agent, which may (but need not) be an aluminum compound. In
24 ¦addition, the patent discloses the optional use of Vitamin C (as-
251 corbic acid) as a mucin precipitating agent in combination with an
26 ¦ anti-microbial agent and a chelating agent. The patent, however,
27l does not suggest that any anticariogenic therapeutic effect is
28 achieved as a result of the aluminum compounds in such composi-
29 1 tions. In fact, other essential constituents in the tablets are
30l incompatible with alumimum ions such that they are not therapeu-
31 1I tically available.
32
I -5-
3Q~
In sum, the prior art has not heretofore suggested a
therapeutically effective system which provides biologically
available aluminum in a comestible in the absence of fluoride.
Accordingly, the primary object of this invention is
to provide means for overcoming the disadvantages of the prior
art approaches to reducing the dental caries potential of sugar
containing foodstuffs.
A related objective is to provide an effective aluminum
containing cariostatic additive for use in sweetened comestibles
such as candy.
A further object is to provide anticariogenic
comestibles incorporating aluminum containing cariostatic
additives of the character described.
Another object is to provide anticariogenic
comestibles of the character described which incorporate a
noncariogenic nutritive sweetening system.
A still further object is to provide new anti-
cariogenic candies.
The foregoing and other objects, advantages, and
features of this invention may be achieved by incorporating
in comestibles anticariogenically effective and nontoxic
amounts of a cariostatic additive comprising at least one
soluble aluminum ion containing salt and a member selected
from the group consisting of adipic acid, ascorbic acid,
and mixtures thereof. Where such an additive is provided in
a candy product, even very low levels of additive (e.g.,
amounts of aluminum as low as about 100 ppm) are effective
since repeated ingestion of small amounts of the anticariogenic
agent has been shown to have an accumulative effect.
~ -- 6
, ~
lr39630~
1 Desirably such additive containing comestib1es also
2 incorporate a noncariogenic nutritive sweetener comprising a mix-
3 ¦ ture of at least one first sweetening agent selected from the group
4I consisting of sorbitol, xylitol and mixtures thereof and at least
o~e second sweetening agent selected from the group consisting of
1~ ~eX ~ rOs~
6 ~cet~se, fructose and mixtures thereof. The mixture contains at
7 least about 75% of the first sweetening agent by weight of the
8 mixture where dextrose is the second agent and at least about 60%
9 of the first agent where fructose is the second agent. The sweet-
ener is provided in the comestible in an amount effective to
ll sweeten it.
12 Use of the cariostatic additive of this invention reduces
l~ ¦ the acid solubility of dental enamel and, where the sweetening
14¦ system of this invention is also employed, there are obtained
products which, when introduced into the mouth, exhibit: little or
16 no harmful lowering of the dental plague pH (indicating that the
17l formation of decay causing oral acids has been minimized)i little
or no harmful decalcification of the dental enamel (decalcification
19 I being a precursor of dental caries formation); and rapid oral
clearance.
22 DET ILED DESCRIPTION OF THE PREFERRED EMBOLI~ENTS
I In accordance with this invention, comestibles, especi-
25 ¦ ally sweetened comestibles such as candy, have incorporated therein
261 anticariogenically effective and nontoxic amounts of an additive
I comprising a mixture of one or more soluble aluminum ion containing
281 salts and a member selected from the group consisting of adipic
291 acid, ascorbic acid, and mixtures thereof.
31 11
1l -7-
1~9(i30~i 1
1~ As used herein, the term "comesti~le" should be understood
2 ¦ to mean substantially any of the wide range of food products suit-
3 ¦ able for ingestion by humans, including without limitation candies,
4 ¦ bakery products, chewing gum, prepared beverages, fruit preparations,
5 ¦ and the like.
61 As used herein, the term "ascorbic acid" should be under-
7 ¦ stood to encompass its isomeric epimer, isoascorbic acid, also known
81 as erythorbic acid and D-erthro-hex-2-enonic acid qamma-lactone~
9¦ which may be substituted for it for purposes of this invention.
o¦ The adipic and/or ascorbic acid may be present at any
11 convenient level greater than 0 up to about 6% by weight of the
12 comestible. Preferably, the acid is present at a level of about 3%
by weight.
14 The particular soluble aluminum salt employed is not
critical, and substantially any nontoxic water soluble aluminum ion
16 containing salt may be used. Suitable aluminum salts include alu-
17 minum potassium sulfate, AlK(S04)2.12H2O; aluminum chloride,
1~ AlC13.6H2O; aluminum sodium sulfate, AlNa(SO4)2.12H2O; aluminum
19 ammonium sulfate, AlNH4(SO4)2.12H2O; aluminum sodium phosphate,
20 ¦ NaA13H14 (P04)8.4H20; aluminum sulfate, A12(SO4)3.18H2O; aluminum
21 nitrate, Al(NO3)3 and sodium aluminate, NaA102. Aluminum potassium
22 sulfate and aluminum sodium sulfate are preferred by reason of their
23 wide availability and established safety.
24 The anticariogenically effective and nontoxic amount of
25 ¦ the soluble aluminum salt should lie in the range capable of sup-
26 ¦ plying about lOOppm up to about 1000 ppm aluminum ions, (0.01 - O.lC
27 weight percent, calculated as aluminum ion). Thus, where aluminum
28 potassium sulfate dodecahydrate and aluminum chloride hexahydrate
29 are employed, the respective salts are present in the range of about
30l 0.2 up to about 2% and about 0.1 up to about 1.0% by weight.
31~l~
32 1 -8-
1~63C~6
I The cari~static additlve of this inventi~n may be used in
2 ¦ all types of sweetened comestibles such as hard candies, taffies
3 I and carmels, chocolates and chocolate coatings and in other candy
4 ~ products. Preferably, however, the additive is provided in tab-
5 ¦ leted and cooked hard candies. Where candy products are produced
6 ¦ from a variety of individual constituents (as in candies in which a
7 I cooked sugar based center may be coated with chocolate), the addi-
81 tive of this invention may be employed in one or more of the con-
9¦ stituents or in all of them.
lo¦ An important feature of this invention is the discovery
11 that, in comparison with other conventionally used carboxylic acids
12 such as citric acid and malic acid, ascorbic and adipic acids are
1~ relatively safe and do not decalcify the teeth when present in the
14 mouth during the rapid oral clearance period achieved with the
15 candies of this invention. In addition, these acids (1) do not
16 interfere with aluminum ions as do many other carboxylic acidsi (2)
17 1 help temporarily to reach pH of 3.5-4.5 in the mouth at which
1~ ¦ aluminum ions are most actively incorporated into dental enamel;
19l and (3) open the enamel apatite crystal lattice somewhat so alumi-
num ions may better react with the enamel.
21 I Candy products produced in accordance with this inventon
22 ¦ are essentially the same as prior art candy products with the
23l exception that, by virtue of the addition of the cariostatic addi-
24 tive of this invention, the candy products hereof may be safely
251 consumed without causing or promoting dental caries.
26¦ Thus, anticariogenic candy products produced in accor-
27l dance with this invention may contain usual and customary comple-
2~1 mentary ingredients conventionally found in candy products such as
291 colorings, flavorings, dairy and vegetable fats, foaming agents,
30l~ texturing agents such as crisped rice, nuts, and the like. How-
31 ll ever, certain conventional candy ingredients are undesirable from a
32 ll
,1 _ 9 _
1~9~i3~6
1 ¦ dental standpoint. For example, significant amounts of fats and
2 ¦ texturing agents such as crisped rice may adversely affect the oral
3 ¦ clearance of the candy. Nonetheless, by employing the additive of
4 ¦ this invention, the candies may be rendered less harmful to the
5 ¦ teeth.
6 ¦ Candies produced in accordance with this invention may be
7 ¦ prepared using the manufacturing techniques heretofore employed.
8 ¦ The additive may be added at any convenient point so long as it is
g ¦ present in the final product at the desired level.
lo ¦ The compositions of exemplary anticariogenic candies
11¦ produced in accordance with this invention are given in the follow-
12~ ing examples.
1~ 1
14 ¦ Example I - Tableted Candy
15 ¦ Constituent Parts by Weight
16¦ Sucrose 95.0
17l Adipic Acid 3.0
1~ Aluminum Potassium Sulfate 0.2
19 Magnesium Stearate 1.0
Flavorings, Colors, etc. 0.8
21
Example II - Cooked Hard CandY
22 Constituent Parts by Weight
23 Sucrose 98.0
Adipic Acid 1.0
26 Aluminum Chloride 0.5
Flavorings, Colors, etc. 0.5
281
29 Desirably, the cariostatic additive of this invention is
301 employed in sweetened comestibles containing, in place of the suc-
I rose or other cariogenic sweetener, a noncariogenic nutritive
31li
32 11
Il -10-
11
9 ~ 3 ~ ~
I sweetlng system comprising a mixture of at least one first sweeten-
21~ ing agent selected from the group consisting of sorbitol, xylitol
3¦ and mixtures thereof and at least one second sweetening agent
4 selected from the group consisting of dextrose, fructose and mix-
tures thereof, with the mixture containing at least about 75% first
6 agent by weight of the mixture where dextrose is the second agent
7 and at least about 60% of the first agent where fructose is the
8 1 second agent.
9¦ Sorbitol is the preferred first agent, with dextrose being
o¦ the preferred second agent on the basis of cost and availability.
11¦ Desirably, homogeneous mixtures of the first and second agents are
12~ employed.
1~ ¦ Where sorbitol-dextrose or xylitol~dextrose mixtures are
14 ~ employed, a 75% sorbitol and/or xylitol - 25% dextrose mixture is
15 ¦ preferred. Where fructose is employed, somewhat greater amounts of
16 1~ the second sweetening agent may be employed. Thus, about 40% fruc-
17 Il trose is preferred in the case of sorbitol-fructose and xylitol-
! fructose mixtures.
19ll Generally, the sweetening mixtures of this invention are
20 ¦ employed at the same levels that the sugar or other cariogenic
Zl sweetening systems have been employed. Thus, where noncariogenic
22 nutritive sweetening systems are employed in accordance with this
23 invention in a candy product they are used preferably at a level of
24 about 40-100% by weight of the candy product.
251 Candy products produced in accordance with this invention
26 ¦ are essentially the same as prior art candy products with the excep-
27 tion that, by virtue of the addition of the cariostatic additive and
28 the substitution of the noncariogenic nutritive sweetening system,
29 they may be safely consumed with a reduction of the incidence and
30 1! severity of dental caries.
31l~
Il --11--
1~)96306
I Candies produced in accordance with this invention may be2 prepared using the foregoing noncariogenic nutritive sweetening
3 system heretofore employed. Manufacturing techniques are generally
4 the same although certain modifications must be made by reason of
5 the use of sorbitol or xylitol as the principal constituent of the
6 sweetening system.
7 Thus, in the case of tableted candies, the same techni-
8 I ques of mixing the ingredients and forming them into tablets are
g ¦ used, but somewhat greater humidity control must be exerted because
lo~ sorbitol and xylitol are desiccants. An agent such as magnesium
11 stearate may also be added at low levels to facilitate removal of
12 the tablets from the mold.
15l With knowledge of these properties of the sorbitol and/or
14 xylitol containing sweetening agents, one skilled in the art can
15 readily adapt existing candy processing techniques to the prepara-
16 tion of other candy products pursuant to this invention.
17 1 The compositions of exemplary anticariogenic candies
lB ¦¦ produced employing the nutritive sweetening system in accordance
19ll with this invention are given in the following examples.
20 1~
21 j Example III - Tableted Candy
I J
22 ~ Constituent Parts by Weiqht
23 I Sorbitol 71.3
2~ Dextrose 23.8
Flavorings, Color, Etc. 0.7
26 Adipic Acid 3.0
28 Aluminum Potassium Sulfate 0.2
29 Example IV - Tableted Candy
Constituent Parts by Weight
30 ll Sorbitol 81.0
31 l¦ Dextrose 14.0
32 1
1~ -12-
I
i3~i
1 Ascorbic Acid 3 0
2¦l Flavoring, Color, etc. 0.5
3 j~ Aluminum Chloride 0.5
4 I Magnesium Stearate 1.0
6 Exa ple V - Tableted Candy
7 Constituent Parts bY Weight
8 Sorbitol 57.2
g Fructose 38.1
Adipic Acid 1.5
11 ¦ Ascorbic Acid 1.5
12 I Flavoring, Color, etc. 0.5
15 I Magnesium Stearate 1.0
14 l~l Aluminum Potassium Sulfate 0.2
15 1I Example VI - Tableted Candy
16¦~ Constituent Parts bY Weiqht
17 ll Xylitol 72.0
1~¦ Dextrose 24.0
19¦ Adipic Acid 3.0
20¦ Flavoring, Colors, etc. 0.2
21 ¦ Magnesium Stearate 1.0
22 ~ Aluminum Chloride 0.5
23 ¦ Example VII - Tableted Candy
25 ¦ Constituent Parts bY Weiqht
26 I Sorbitol 64.1
Dextrose 15.5
27 ~ Fructose 15.5
28 1¦ Adipic Acid 1.5
¦ Ascorbic Acid 1.5
30l Flavorings, Colors, etc. 0.5
311j Magnesium Streate 1.0
32 '
! Aluminum Chloride 0.5
-13-
3C~
¦i Example VIII - Tableted Candy
li
2¦¦ Constituent Parts by Wei~
3¦¦ Sorbitol 35-7
4 Xylitol 35.7
Dextrose 23.8
6 Adipic Acid 3.0
7 Falvoring, Colors, etc. 0.2
8 Magnesium Stearate 1.0
9~l Aluminum Chloride 0.5
10 1!
11l Example IX - Cooked Hard CandY
12 ¦ Constituent Parts bY Weight
15 1I Sorbitol (70% solution) 81.8
l4~1 Dextrose 17.3
15~ Adipic Acid 0.8
ll Falvoring, Color, etc. 0.2
16ll Aluminum Potassium Sulfate 0.2
17!l
~ Example X - TaffY
19 I Constituent Parts b~Y Weight
20 I Sorbitol (70% solution) 70.1
21 j Dextrose 16.3
22 Egg albumin ~45.27% solution) 2.4
23 92 degree coconut oil 8.9
24 Adipic Acid 1.7
Sodium Alginate 0-3
26 Calcium Acetate 0.1
27l Emulsifier 0.1
28l Flavoring, Color, etc. 0.2
29~ Aluminum Chloride 0.5
51
32 1!
li -14-
!l
ll 10~3~
Example XI - Chocolate Candy Coating
2~ Constituent Parts by Wei~ht
3¦ Sorbitol 42.0
4 1 Dextrose 14.0
51 Kaomel (hard butter) 30.9
61 Cocoa Powder 7.8
7 ¦ Non-Fat Dry Milk 4.2
8¦ Lecithin 0-3
g Salt 0.1
Vanilla Powder 0.9
11 Aluminum Potassium Sulfate 0.2
12
EXPERIMENTAL EVALUATIONS
14 1 The anticariogenic attributes of the products produced in
15 I accordance with this invention have been verified by the following
7 1 experimental studies.
A primary criterion in evaluating an anticariogenic agent
is its ability to reduce the solubility of dental enamel, namely,
1l enamel solubility reductions ("ESR"). In vitro "ESR" studies are
Il carried out in the following manner. Sound bovine incisors are
¦ mounted in self-curing acrylic resin, with the labial surface
I exposed, and given a thorough prophylaxis with flour of pumice. A
23 "window" is then formed on the labial surface by dripping wax over
24 a 1.0 cm diameter aluminum foil circle. A sharp stylus is then
used to circumscribe the foil wndow which is then pulled off expos-
26 ing a round area of enamel of reproducible size.
27 The windowed teeth are decalcified 4 consecutive times
28 over 20-minute intervals with 25 mls aliquots of a 0.2 N acetic
29 acid solution (buffered to a pH of 4.0) at a stirring rate of 60
50 1! rpm using an ESR stirring apparatus. By the 4th decalcification,
31
5 2
Il -15-
1g;~963C}~
1 the amount of calcium and phosphorus being demineralized from the
2 teeth has reached a constant level. The teeth are then treated
3 with 25 mls of candy supernatant (1 part candy diluted with 3 parts
4 redistilled water to simulate the d:ilution that occurs in the mouth
upon ingestion) stirred at a rate of about 60 rpm.
6 After treatment, the teeth are decalcified again with 25
7 ml portions of the acetic acid buffer for four additional 20-minute
8 intervals. The 5th and 8th decalcification solutions are referred
g to as the first post-treatment decalcification (lst PTD) and 4th
lo post-treatment decalcification (4th PTD), respectively.
11 The difference in the amount of calcium and phosphorus in
12 the 4th decalcification solution before treatment and that present
1~ in the 5th and 8th decalcification solutions after treatment,
14 divided by the amount of the 4th decalicification, times 100 is
15¦ used to determine the 1st PTD and 4th PTD ESR values. Calcium is
16¦ determined using atomic absorption spectroscopy, and phosphorus
17l using the Fiske-Subbarow method.
l~I In order to demonstrate that repeated ingestion of candy
19 incorporating the cariostatic additive of this invention over short
periods of time has an accumulative effectiveness in reducing the
21 I solubility of dental enamel, the teeth are treated a number of
22 ¦ times of relatively short duration (e.g., 5 minutes, the typical
23 oral clearance time of candies of this type). Using this technique,
24 a grape flavored tableted candy having the formulation given in
Example III was evaluated. For comparative purposes a candy of the
26 same formulation but without the aluminum salt was tested as a
27 control. The ESR data for the Example III candy was measured after
28 10 five minute treatments and also after 20 five minute treatments.
29 The ESR data, which are given in Table I, show that repeated 5-minute
treatments with this dissolved candy causes an accumulated signifi-
31 ¦¦ cant ESR effect. After 20 such treatments an ESR of 70% is obtained.32 1
!I -16-
~09~63~i
21~ TABLE I
3 11
ll No. of 5-Min. ~A ESR (%) P ESR (%)
4 I Treatment Solution Treatments 1st PTD 4th PTD 1st PTD 4th PTD
I ~
5 ¦ Example III, but no
¦ AlK(S04)2.12H 0
61 (pH adJusted to 4.0)
7 ¦ (Average of 3 readings) 20 9 5 12 3
81
l Example III
9 (pH adjusted to 4.0)
(Average of 3 readings) 10 41 30 44 25
11
Example III
12 (pH adjusted to 4.0)
(Average of 3 readings) 20 69 43 74 43
14
While ESR evaluations are indicateive of the effective-
16 ~ ness of an anticariogenic agent, it is also very desirable to
17 1l determine the amount of the agent actually taken up by the dental
enamel in order to further establish its efficacy. Six windowed
1911 sound bovine incisors were treated with the candy of Example III
201~ diluted 1:3 with redistilled water. The teeth were treated 20
21 consecutive times over separate 5 minute intervals with 25 mls of
22 the candy solution. After treatment the teeth were decalcified for
23 30 seconds in 15.0 mls of 2.0 HC104, and the amount of calcium and
24 aluminum was determined. Calcium was determined by atomic absorp-
tion, and alumlnum by the Aluminon method.
26 The data which are reported in Table II unequivocally
27 demonstrate that a substantial amount of aluminum ion reacts with
28 and is taken up into the tooth enamel. Treatment of teeth with
29l redistilled water in a similar manner resulted in a zero aluminum
30l uptake score. These accumulative aluminum uptake values correspond
31
32 l
Il -17-
3~
I
1 to and should be associated with the accumulative ESR values re-
2 ¦ ported in Table I. Collectively they demonstrate the cariostatic
3 ¦ effectiveness of the additives of this invention.
4 l
6 TABLE II
l Calcium Total g Aluminum Total g g Aluminum/
7 1 Tooth Ion ppm Calcium Ions ppm Aluminum g Calcium xlO 3
8 1 1 1.14 1710 0.79 11.85 6.93
9 1 2 0.89 1335 0.50 7.50 5.62
10 1 3 0.68 1020 0.54 8.10 7.95
11 1 4 1.22 1830 0.88 13.20 7.21
12 5 0.97 1455 0.88 13.20 9.07
6 1.00 1500 0.97 14.55 9.70
The anticariogenic effectiveness of the additives has
also been shown in an in vivo rat study conducted as follows. Ten
Il 35-day old Wistar strain rats were randomly distributed into two
1~ equal groups according to sex, body weight, and littermates. Group
l9 2 rats served as the control and were fed a low fluoride corn meal
diet and fluoride free water ad libitum. Group 1 rats were main-
21 tained on the same regimen except that their corn diet was supple-
22 mented with 3% adipic acid and 1% AlC13.6H20. At the end of 1
month, the rats were sacrificed, and the acid solubility of their
mandibular molars was measured. The data are reported in Table
24 I III.
25 l
26 ¦ TABLE III
21 Phosphorous ESR Calcium ESR
28 Group Reps. Mean + b Mean + b
No. (N) S.D. (ppm) Reduction -S.D. (ppm)Reduction
29
1 10 2.05+0.20 40.2 4.40+0.40 35.8
- (P S) - (P S)
31 2 10 3.43+0.20 ---- 6.85+~.68 ----
32
Il -18-
1~363(~6
2 These data show phosphorus and calci~m ESR's of 40% and 35%, re-
s spectively, for rats fed a diet inco:rporating the cariostatic
4 ~ additive of this invention.
5 ¦ The anticariogenic effectiveness of the anticariogenic
6 ¦ candies of this invention has also been demonstrated in rats using
7 I the method described by Francis, "The Effectivenss of Anticaries
8 ¦ Agents in Rats Using an Incipient Carrious Lesion Method", Arch.
g Oral Biol., 11:141-148 (1966).
oI A total of 100 weanling (21 day old) Wistar strain rats
were randomly divided into five equal groups according to sex, body
2 1 weight, and litter mates. The parents of the weanlings were placed
on a noncariogenic low fluoride corn diet and fluoride-free re-
4 I distilled drinking water one week prior to mating. The dames were
I maintained on this same regimen during the pups' 21-day gestation
16~ period, birth, and 21-day weaning period in order to avoid exposure
17 1 of the pups to any exogenous sources of fluoride during their
1~¦ development. After weaning, the 21-day old rats were placed on a
19¦ high sucrose caries inducing diet and fluoride-free redistilled
201 water ad libitum. Once daily, five days per week for a 4 week
I period, both the right and left molars of the mandibular were each
211 swabbed for 60 seconds with the respective topical anticariogenic
23 candy solution. A stick cotton swab was used to apply the solution
l to the molars by freshly dipping into the candy solution at 15
24I second intervals. The topical candy solutions used for treatment
261 were prepared by dissolving the various experimental candes 1 part
l by weight with 3 parts redistilled water. The basic candy formula
281 Example IIIwas employed wth the following variations:
29~ Group 1 - Control group - Example III without the AlK(SO4)2.
l 12H20
31l Group 2 - Example III
32 1I Group 3 - Example III with 6% AlK(SO4)2.12H20
I'l -19-
1 1~963~6
1 Group 4 - Example III substituting dextrose for all of
2 the sorbitol
3 Group 5 - Same as Group 3, substituting dextrose for all
4 the sorbit:ol
51 The rats were housed in an air-conditioned room in cages
61 with raised screen floors, and the usual sanitary measures in the
7I care of laboratory animals were strictly followed. The lights were
81 time regulated to insure 12 hours of light and 12 hours of dark-
9¦ ness.
o¦ The weight of the rats was determined initially and then
11¦ at the end of the one-month study. There were no statistical
12 differences in weight gain between the experimental groups and the
15I control group. In addition, not one single animal died during the
14 1 course of the study.
15 ¦ At the termination of the experiment the animals were
16¦ sacrificed by chloroform inhalation, and the teeth were stained
17 ~ with 1% silver nitrate, sectioned in half and graded for incipient
18 lesions. The data are reported in Table IV.
19
TABLE IV
21 Incipient Lesions
22 Group No. IncidenceReduction Se~,~erity Reduction
23 1 (Control) 27.3+1.6 ---- 58.4+5.8 ----
24 2 24.4+2.510.6% 52.6+5.59.9%
2s 3 22.4+2.517.9% 49.7+6.114.9%
4 24.5+3.510.3% 57.0+10.23.0%
26 5 25.4+3.67.0% 57.6+12.21.4%
27
28 A statistical analysis of the data showed that the 11%
29 caries incidence reduction noted for Group 2 (3:1 sorbitol-dextrose
candy containing .2% AlK(S04)2.12H20) was significant at the 98%
31
32 1
!1 -20-
963~
I
1 ~ confidence level, while the 18% reduction obtained with Group 3
2 ¦ (3:1 sorbitol-dextrose candy containing 6% AlK(S04)2.12H20) was
3 ¦ significant at the 99% level. The 10% and 7% reductions noted for
4 ¦ Groups 4 and 5 respectively were not statistically significant.
5 ¦ These latter two groups were identical to Groups 2 and 3 respec-
6 ¦ tively except that all the sorbitol in the candies was replaced by
7 ¦ dextrose. While Group 4 had, on the average approximately the same
81 number of lesions as Group 2, the lesions of Group 4 were much more
9¦ severe. The data demonstrate that the 3:1 sorbitol-dextrose candies
o¦ containing AlK(S04)2.12H20 have a significant effect in reducing
11¦ dental caries in vivo. They also demonstrate that all candies are
12¦ to a degree benefited by the cariostatic additive system of this
invention.
14 1 The criticality of the use of adipic and/or ascorbic acid
15 ~ in combination with the aluminum salt has also been verified experi-
16¦ mentally. Windowed bovine teeth were treated using the described
17 1 ESR method, except that the teeth were given a single 20 minute
1~¦ treatment with solutions containing 37 ppm aluminum ions (supplied
19 as AlK(S04)2.12H20) with 1% by weight of various carboxylic acids
20 ~ with pH adjusted to 4Ø Calcium and phosphorus ESR data are given
21 ¦ the Table V and show that, in contrast to other acids which deacti-
22 ¦ vate aluminum or significantly reduce its effectiveness as an
231 enamel solubility reducing agent under these conditions, adipic and
24 I asorbic acids have a minimal effect, especially at the 4th post
26 treatment decalcification and are compatible with aluminum.
27
28
29
32 11
Il -21-
1~963~
1 TABLE _V
Phosphorus ESR (%) Calcium ESR (%)
3 37 ppm aluminum Mean (+ S.D.) Mean (+ S.D.)
4 With 1h of 1 PTD l~t l~
5 No Acid 92.1 ( 5.0) 72.2 (+18.5) 90.4 (_ 6.0) 75.7 (+15.5)
6 ¦ Adipic Acid 85.7 (_ 5.8) 72.7 (+, 8.9) 81.7 ( 4-0) 70.7 (+ 8.6)
7 ¦ Asocorbic Acid 80.7 (_ 6.8) 70.7 (+12.8) 78.7 (+ 6.7) 72.1 (+10.3)
8 ¦ Glutaric Acid 77.9 (_ 5.2) 65.1 (_ 5.7) 70.0 ( 5.8) 64.1 ( 5.7)
9 ¦ Succinic Acid 71.5 (_12.5) 54.4 (+11.5) 64.3 (+10.8) 57.5 (+ 7.5)
10 ¦ Fumaric Acid 65.6 (_ 2.9) 52.2 (+ 5.6) 60.9 (+ 5.8) 52.4 (_ 8.4)
11 ¦ Tartaric Acid 7.9 ( 34.7) -25.2 (_54.0) 3.5 (+23.8) -15.5 (_41.4)
12 ¦ Citric Acid 11.4 (_ 6.8) -10.9 ( 10.7) 7.5 ( 8.7) - 8.8 (+10.3)
15 ¦ Malic Acid-12.5 (+26.6) -11.3 ( 17.7) -16.0 ( 22.4) - 6.3 (+16.0)
14 1
15 ¦ Control-Redistilled
16 ~ 2 -12.5 (_ 8.1)-26.4 (+,21.9)- 2.6 (+ 8.4)- 4.7 (+ 5.9)
17 l~ While the foregoing invention has been described with
1~ respect to candy products in particular, these technigues are
19l intended to and have utility in relation to other food products in
which the invention additive may be employed.
23
24
26
28ll
29
31
32 11
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