WO2002100181A2

WO2002100181A2 - Sugar-based composition containing caseinoglycomacropeptide

Info

Publication number: WO2002100181A2
Application number: PCT/EP2002/005830
Authority: WO
Inventors: Jean-Richard Neeser; Bernhard Guggenheim; Edward Brian Fern
Original assignee: Societe Des Produits Nestle S.A.
Priority date: 2001-06-08
Filing date: 2002-05-27
Publication date: 2002-12-19
Also published as: WO2002100181A3; PE20030101A1; AU2002345773A1

Abstract

The invention relates to a sugar-based composition which contains caseinoglycomacropeptide and/or its derivatives, said product having a beneficial impact on oral health, and in particular an inhibitory effect on caries and dentinal fissure lesions.

Description

Sugar-based composition containing caseinoglycomacropeptide

Field of the invention

The present invention relates to a food product or a beverage, and in particular a sugar-based composition having a beneficial effect on the health of the oral cavity, especially by inhibiting or decreasing incidence of lesions such as caries or dentinal fissures.

Background of the invention

Some products derived from milk are of great interest for oral health. Thus, anticariogenic properties are recognized for casein in certain forms and for some of its derivatives. A few cheeses, for example, are known for their anti-caries activity (Nutrition Reviews, 46, 215-217, 1988; Pause, B. and Lembke, J., Milchwissenschaft, 42, 697-700, 1992; Pause, B. and Lembke, J., Milchwisssenschaft, 48, 137-141, 1993).

In patent US 5427769 (Nestec S.A.), the appearance of dental caries is prevented by placing in contact with the teeth a food composition containing micellar casein in a sufficient quantity to inhibit colonization by Streptococcus sobrinus, the principal bacterial agent involved in carious pathology.

Patent EP 748591 (Societe des Produits Nestle S.A.) also describes the use of fluorinated micellar caseins or their micellar subunits for treating plaque or dental caries.

Patent US 4992420 (Nestec S.A.) describes the treatment of the buccal cavity with κ-caseinoglycornacropeptides (CGMP) derived from whey in order to eradicate dental plaque and caries. Likewise, patent US 4994441 (Nestec S.A.) describes an anti-plaque and anti-caries composition in which the active agent is chosen from K-caseinoglycopeptides. In confectionery, in order to reduce the incidence of caries, it is known to replace sugars with polyol, e.g. sorbitol, mannitol, maltitol or xylitol. Nevertheless, such "sugarless" products do not have the same organoleptic properties as sugar-based confectionery.

In other types of food products or beverages (infant formulas, nutritional products for children, composition for clinical nutrition) femientescible sugars are strictly required as a source of energy, growth and/ or maintenance. In such cases "sugarless" products are not envisionable.

Although the anticariogenic properties are recognized for casein in certain forms and for some of its derivatives, there is no indication in the prior art on the effect of CGMP when associated with confectionery products, or other sugar-based products.

Summary of the invention

Accordingly, in one aspect, the invention relates to a sugar-composition which contains caseinoglycomacropeptide and/or its derivative, said product is intended for improving the health of the oral cavity, and particularly it has an inhibitory effect on caries and dentinal fissure lesions.

In fact, it has been surprisingly found that CGMP, when present in a sugar-based product, was able to display a significant inhibition in dentinal fissure lesions and caries incidence.

In another aspect, the invention relates to the use of caseinoglycomacropeptide and/or its derivatives in the preparation of sugar-based composition intended for improving the health of the oral cavity. hi another aspect, the invention provides a method of preventing or reducing caries and dentinal fissure lesions consisting of providing to the consummer a sugar- based composition containing caseinoglycomacropeptide and/or its derivatives.

The compositions of the present invention have a beneficial effect on the health of the oral cavity, by preventing or reducing dentinal fissures and caries.

Detailled description

Within the following description, CGMP refers to caseinoglycomacropeptide and/or its subcomponents and/or its bioactive hydrolytic products.

Caseinoglycomacropeptides (CGMPs) may then be used in the sugar-based composition in any suitable form, including salts of calcium, sodium or potassium, for example. It is preferably used as such, or encapsulated.

CGMP can be obtained by an ion-exchange treatment of a liquid lactic raw material containing CGMP. Suitable starting materials of lactic origin may include for example: - the product of the hydrolysis with rennet of a native casein obtained by acidic precipitation of skimmed milk with a mineral acid or acidifying ferments, optionally with addition of calcium ions, the hydrolysis product of a caseinate with rennet, a sweet whey obtained after separation of casein coagulated with rennet, - a sweet whey or such a whey demineralized, for example, by electrodialysis and/or ion exchange and/or reverse osmosis, a concentrate of sweet whey, a concentrate of whey proteins obtained by ultrafiltration and diafiltration of sweet whey. - mother liquors ofthe crystalhzation of lactose from a sweet whey, a permeate of ultrafiltration of a sweet whey. The method preferably used to prepare CGMP is described in WO 98/53702 and consists in the decationization of the liquid raw material, such that the pH has a value of

1 to 4.5, bringing the said liquid into contact with a weak anionic resin of hydrophobic matrix, predominantly in alkaline form up to a stabilized pH, then separation of the resin and the liquid product which is recovered, and desorption of CGMP from the resin.

The amount of CGMPs in the product may be of about 0.01% to about 10% by weight on dry matter, and preferably about 5% by weight on dry matter.

The composition is preferably a confectionery such as a sweet, a high boil, a chew, a tablet, a gum, or it may be a biscuit, a chocolate tablet, or any combination to give a composite product. It may also be a sweetened beverage, a milk powder, an infant nutrition product, a clinical nutrition composition.

The sugar-based composition may contain a flavour, the flavour may be a fruit flavour, eg. Strawberry, rasperry, orange, lemon or any other flavour such as mint, etc. The amount of flavour in the composition may be from 0.5% to 10% and preferably from 1 to 3% by weight based on the total weight of the product.

The product of the invention is preferably a pressed acid tablet, e.g. similar to

Polo.

Other ingredients of the products are conventional as follows:

For high boils, bulk sweeteners such as sucrose and glucose syrup normally comprise about 95-98% of the product. The high boils may be prepared by boiling the ingredients of a high-boiled sweet to give a syrup, further heating the syrup to reduce the moisture content to below 5% by weight based on the weight of the syrup, adding a flavour to the syrup with mixing, deposited the syrup in moulds and the syrup cooled preferably to room temperature, e.g. from 20°C to 30°C, to solidify the high-boiled sweet. For chews such as caramel, toffee and fudge, the basic ingredients are sugar, glucose syrup, milk, milk protein, fat, salt and water. The chew may be prepared by conventional methods. For example, the ingredients may be blended to form syrup, then cooked, shaped and, if necessary, dried.

Tablets are characterised by being hard and somewhat brittle with a smooth surface and differ from hard candy in that they are formed by compressing a tablet base powder in a die where the particles bond together under pressure and the compacted tablet is ejected from the die. The tablet base material is preferably a sugar, e.g. sucrose, fructose, dextrose. Tablets may be chewed in a crumbly state and eventually swallowed.

Gums consist of sugar and hydrocolloids and include hard, soft and foamed gums, tubes and corrugated strips, jujubes, fruit leathers, lemon slices, pastilles, gummy bears and jelly babies. The amount of hydrocoUoid may be from 0.1% to 5% preferably from 0.25% to 4% by weight based on the weight of the gum. The hydrocoUoid may be agar, xanthan gum, locust bean gum, gellan gum, gum arabic, pectin, gelatine, kappa- carrageenan, guar gum, or modified or unmodified starches. They may be prepared by conventional methods, e.g. the ingredients may be blended to form a syrup, then cooked, shaped, if necessary, dried.

Biscuits consist of wheat flour, vegetable fat, syrup, sugars and raising agents. The amount of wheat flour may be from 20% to 80%, preferably from 40 to 70%. The amount of sugar may be from 80% to 5%, preferably from 10 to 30%. Biscuits may be prepared by conventional methods, e.g. the ingredients may be mixed to form a dough, then shaped and baked.

The sugar-based compositions of the present invention have a beneficial effect on the health of the oral cavity, in particular by preventing or reducing dentinal fissures and caries. The following examples are given by way of illustration only and in no way should be construed as limiting the subject matter of the present application. Percentages and parts are by weight unless otherwise indicated.

Example 1: Effect of caseinoglycomacropeptide (CGMP) in the presence of sucrose in a confectionery product on plaque extent and caries incidence.

Materials and methods

The study was conducted on 10 litters of Osborne-Mendel rats, each litter consisting of 6 pups. Thirteen days after birth the pups and their dams were transferred to stainless-steel screen-bottom cages without bedding and fed a finely ground stock diet (diet No. 890, Nafag AG, Switzerland) to prevent impaction of food and bedding particles in fissures. Tap water was given ad libitum.

On day 20 after birth, the dams were removed and the rats were offered, ad libitum, the modified cariogenic diet 2000a containing 25% sucrose and a soybean- protein-based substitute for skim milk, and drinking water as described below.

On days 21 and 22, each rat was infected orally, twice daily, by inoculation of

100 microliters of heavy suspensions of Streptococcus sobrinus OMZ 176 and

Actinomyces viscosus Ny 1 (ca. 10 per ml). To support the implantation of these bacteria, all rats received, ad libitum, drinking water containing 2% glucose and 2% sucrose as well as the milk-protein-free cariogenic diet 2000a from day 20 until day 23.

On day 23, littermates were distributed among the 6 treatments, 1 animal per cage, in the programmed feeder and began to receive the daily 36 meals as indicated in the list of treatments. Treatment groups 1-3 were offered, over a 12 hour period, a powdered preparation corresponding to 12 Sugar sweet, available under the brand name POLO (POLO is a registered hade mark of SOCIETE DES PRODUITS NESTLE S.A. of Switzerland) and prepared so that the test meals contain 0, 5 and 10% CGMP respectively and 24 low cariogenic meals, containing 10% sucrose and a soybean-based substitute for skimmed milk (modified diet 2000a). The feeding regime consisted of 1 test meal followed by 2 low cariogenic meals at 20 minute intervals.

Treatment groups 4-6, were identical with the above except that the intervening meals contained 20% sucrose instead of 10%. Drinking water was available ad libitum, throughout the experimental period.

The feeding program commenced at 10.1 Oh with the first meal and ended with the last meal at 21.50h. This feeding regime, which continued for 46 days until day 69, is shown in the table of feeding times.

At the end of the 46-day experimental period, the animals were sacrified.

Erythrosin stained maxillary molars were evaluated for plaque extent using the method described by Regolati and Hotz (1972) and mandibular molars were sectioned and scored for fissure caries (Kόnig et al., 1958). Data were compared with a two-way analysis of variance and least significant differences calculated.

The active phase during which the rats eat is during the hours of darkness i.e. 18h00-6h00. In order to allow refilling of the food cups during normal working hours, the circadian biorhythm was stepwise reversed between days 16 and 19 by advancing the active phase of the rats 4 hours each day. On day 16/17 the begining of the active period was brought forward from 18.00h to 15.00h i.e. it was night from 15.00h - 03.00h onwards. On day 17/18 the begining of the active period was brought forward from 15.00h to 12.00h i.e. it was night from 12.00h- OO.OOh and day from 00.00 onwards. Finally, on day 18/19 the begining of the active period was brought forward from 12.00h to lO.OOh i.e. it was night from lO.OOh - 22.00h onwards. Therefore, by day 19 the shift of the active phase for the rats from the hours of darkness to normal working hours (lO.OOh - 22.00h) was completed.

COMPOSITION OF THE DIETS OFFERED

1) COMPOSITION OF THE MILK-PROTEIN-FREE CARIOGENIC DIET 2000 a (Offered to all rats during the association period i.e. days 20-23)

Wheat flour 39% Soybean-based substitute for skim milk * 28%

Powdered sucrose 25%

Brewer's yeast 5%

Gevral protein 2%

Sodium chloride 1%

* composition of the soybean-based substitute for skim milk

Soya protein extract (SUPRO-PP 1611) 2130 g

D(+) - Lactose Monohydrate 2670 g

Calcium chloride dihydrate (CaC12 - 2 H2O) 40 g L-Methionine (C5Hl lNO2S) 18 g

L-Lysine (C6H14N2O2- HC1) 6 g

2) COMPOSITION OF THE MILK-PROTEIN-FREE LOW

CARIOGENIC DIET 2000 a (Offered to rats in treatment groups 1-3 during the test period - 2 low cariogenic meals offered for every Polo Sugar test meal)

Wheat flour 54 %

Soybean-based substitute for skim milk 28 %

Powdered sucrose 10 % Brewer's yeast 5 %

Gevral protein 2 % Sodium chloride 1%

3) COMPOSITION OF THE MILK-PROTEIN-FREE CARIOGENIC

DIET 2000 a (Offered to rats in treatment groups 4-6 during the test period - 2 meals of cariogenic diet offered for every Polo Sugar test meal)

Wheat flour 44 %

Soybean-based substitute for skim milk 28 %

Powdered sucrose 20 % Brewer's yeast 5 %

Gevral protein 2 %

Sodium chloride 1%

TREATMENTS (DAILYi

1- Sugar Polo 0% CGMP 12 x 400 mg test powder

24 x 200 mg of milk-protein-free low cariogenic diet (10% sucrose) ( 1 test meal followed by 2 low cariogenic meals)

2- Sugar Polo 5% CGMP 12 x 400 mg test powder

3- Sugar Polo 10% CGMP 12 x 400 mg test powder

4- Sugar Polo 0% CGMP 12 x 400 mg test powder 24 x 200 mg of milk-protein-free cariogenic diet (20% sucrose) ( 1 test meal followed by 2 low cariogenic meals)

5- Sugar Polo 5% CGMP 12 x 400 mg test powder

24 x 200 mg of milk-protein-free cariogenic diet (20% sucrose) ( 1 test meal followed by 2 low cariogenic meals)

6- Sugar Polol0% CGMP 12 x 400 mg test powder

TABLE OF EATING TIMES

Cariogenic (10% and 20%) Meals Polo Sugar Meals

10.10 (first meal) 10.30

10.50

11.10 11.30 11.50

12.10 12.30 12.50

13.10 13.30 13.50

14.10 14.30 14.50

15.10 15.30 15.50

16.10 16.30 16.50

17.10 17.30 17.50

18.10 18.30 18.50 19.10 19.30

19.50

20.10 20.30

20.50

21.10 21.30

21.50 (last meal)

RESULTS

The results are shown in Table I.

• Smooth surface plaque extent (pe)

There were no significant differences in smooth surface plaque extent between any of the treatment groups.

• Initial dentinal fissure lesions (t)

Comparisons between groups containing 10% sucrose (trts 1-3)

The groups containing 5 and 10% CGMP (trts 2 and 3 respectively) did not significantly affect the incidence of T lesions compared with the control group (trt 1) neither were the two groups significantly different from each other,

Comparisons between groups containing 20% sucrose (trts 4-6)

As above, no significant differences in T lesion development were observed between the CGMP groups and the control or between the two CGMP treatments.

Comparisons between the 10 and 20% sucrose groups

The control group containing 10% sucrose (trtl) displayed a borderline significant inhibition of T lesion incidence compared with the 20% sucrose control group (trt 4) (PF<0.05) and the group containing 5% CGMP with 10% sucrose (trt 2) showed a more significant inhibition (PFO.01) compared with the corresponding 20% sucrose group (trt 5). The two treatments containing 10% CGMP (trts 3 and 6) were not significantly different.

• Advanced dentinal fissure lesions (b)

Comparisons between groups containing 10% sucrose (trts 1-3)

The groups containing 5 and 10% CGMP (trts 2 and 3 respectively) did not significantly affect the incidence of B lesions compared with the control group (trt 1).

Comparisons between groups containing 20% sucrose (trts 4-6)

The treatment group containing 10% CGMP (trt6) reduced B lesion incidence at the borderline of significance compared with the control group (trt 4) and versus the 5% CGMP group (trt 5) (PFO.05).

Comparisons between the 10 and 20% sucrose groups

As observed for T lesion incidence, the control group containing 10% sucrose (trtl) displayed a borderline significant inhibition of B lesion incidence compared with the 20% sucrose control group (trt 4) (PFO.05). The group containing 5% CGMP with 10% sucrose (trt 2) showed a more significant inhibition (PFO.01) compared with the corresponding 20% sucrose group (trt 5). The two treatments containing 10% CGMP (trts 3 and 6) were again not significantly different.

• Cavitated dentinal fissure lesions (c)

Comparisons between groups containing 10% sucrose (trts 1-3)

The groups containing 5 and 10% CGMP (trts 2 and 3 respectively) did not significantly affect the incidence of cavitated C lesions compared with the control group (trt l).

Comparisons between groups containing 20% sucrose (trts 4-6) A significant inhibition in C lesion development (PFO.01) was observed in fretment group 5 (5% CGMP) versus the control group (trt 4) and a more significant inhibition by treatment group 6 (PFO.001) containing 10% CGMP.

Comparisons between the 10 and 20% sucrose groups

Treatment groups offered 5% and 10% CGMP with a 10% sucrose diet were not significantly different from the 5 and 10% CGMP treatment groups with a 20% sucrose diet. However, the 10% sucrose control (trt 1) displayed a highly significant inhibition in C lesion development (PFO.001) compared with the 20% sucrose control (trt 4).

• Smooth surface caries (e)

Comparisons between groups containing 10% sucrose (trts 1-3)

Compared with the control (trt 1) both groups containing CGMP significantly reduced the incidence of smooth surface E lesions. Treatment 2 containing 5% CGMP reduced E lesions with a borderline significance factor (PFO.05) whereas fretment 3 contaimng 10% CGMP was more effective (PFO.01).

Comparisons between groups containing 20% sucrose (trts 4-6) Treatment 6 containing 10% CGMP inhibited the developement of E lesions with a borderline significance factor (PFO.05) compared with the control (trt 4). Treatment 5 containing 5% CGMP failed to show any significant inhibition.

Comparisons between the 10 and 20% sucrose groups There were no significant differences in E lesion development either between the confrol (trts 1 v trt 4) or between the CGMP treatments in the 10 and 20% sucrose groupings.

• Weight gain (g)

There were no significant differences in weight gain between the treatments.

advanced (B) and cavitated (C) dentinal fissure lesions, smooth surface caries (E) and weight gain (g). = 4 units at risk/ = 12 fissures at risk/ = 20 units at risk ; n.s. = not significant. Treatments 2 and 3 were compared with treatment 1, treatments 5 and 6 were compared with treatment 4. Example 2: Confectionery having caries-protective properties.

The preparation of a tablet sweet comprising sucrose, starch and glucose is carried out by dispersing starch and glucose within the sucrose to obtain sugar granules. 10% by weight of CGMP based on the total weight of the tablet sweet are blended with the sugar granules and flavor, and the mix is tableted by conventional means.

Example 3: Chewing gum

A chewing gum for preventing or treating caries and dentinal fissures is prepared by adding 5 % of CGMP to the following typical ingredients: 67.5 % Sucrose, 20 % Gum base, 5 % Calcium carbonate, 3 % Glycerin, 2 % Pluronic F127, 1 % Cellulose gum, 0.5 % Balast compounds and 1 % Flavor.

Example 4: Confectionery having caries-protective properties

A high boil sweet comprising sucrose and glucose is prepared by blending sucrose, glucose and water together to make a slurry. The slurry temperature is raised to 145°C to give a sugar syrup with a total solid content of 97%. 2.5% CGMP by weight based on the total weight of the high boil sweet are blended with the sugar syrup and flavor, and the syrup is then deposited in moulds to cool down to form the high boil sweet.

Claims

1. A sugar-based composition which contains caseinoglycomacropeptide and/or its derivatives as an active ingredient, said product having a beneficial impact on oral health.

2. A sugar-based composition according to claim 1, which has an inhibitory effect on caries and dentinal fissure lesions.

3. A sugar-based composition according to claim 1 or 2, wherein the caseinoglycomacropeptide is in the form of calcium, sodium or potassium salts.

4. A sugar-based composition according any of to claims 1 to 3, which contains about 0.01% to about 10% caseinoglycomacropeptide and/or its derivatives by weight on dry matter.

5. A sugar-based composition according to any of claims 1 to 4, which is a confectionery such as a sweet, a high boil, a chew, a tablet, a gum, a biscuit, a chocolate tablet, or any combination to give a composite product.

6. A sugar-based composition according to any of claims 1 to 4, which is a sweetened beverage, a milk powder, an infant nutrition product, a clinical nutrition composition.

7. The use of caseinoglycomacropeptide and/or its derivatives in the preparation of sugar-based composition intended for improving the health of the oral cavity.

8. The use according to claim 7, in which the composition is according to any of claims 1 to 6.

9. A method of preventing or reducing caries and dentinal fissure lesions consisting of providing to the consummer a sugar-based composition containing caseinoglycomacropeptide and/or its derivatives.

10. A method according to claim 9, wherein the composition is according to any of claims 1 to 6.