Research method

Development of Anti-Caries Chewing Gum

X-ray diffraction/scattering

Crystallographic visualization of the process of restoration after early-stage caries

Role of SPring-8

Achievements

First observation of crystal-structure changes involving demineralization andremineralization associated with early-stage caries* (tooth decay)
Restoring lost crystals by supplying phosphoryl oligosaccharides of calcium**in cases of early-stage caries
Development and commercialization of anti-caries chewing gum† containing
phosphoryl oligosaccharides of calcium
R&D facility: Ezaki Glico Co., Ltd.
† This anti-caries chewing gum is approved as a Food for Specified Health Use (September 30, 2010)*Early-stage caries: Oral bacteria produce acids from carbohydrates contained in food, and these acids decay tooth crystals composed ofphosphorus and calcium (demineralization). This mineral loss is termed early-stage caries. Remineralization, which refers to the process of restoringminerals lost in demineralization, allows recovery from early-stage caries.
**Phosphoryl oligosaccharides of calcium: Phosphoryl oligosaccharides of calcium is a mineral that can be produced from potato starch. The
compound is highly soluble in saliva. Caries-causing bacteria cannot use this compound to produce acids that cause caries.

BackgroundResults

When early-stage caries advances, the tooth
surface is eroded and tooth cavities (carious pits)
develop. Tooth drilling is required to treat thesecavities; therefore, preventive care such as regular
tooth brushing has been recommended to remove
caries-causing plaque.
Recently, research on regenerating minerals
eroded during demineralization, remineralization,
has been conducted. These studies revealed that
phosphoryl oligosaccharides of calcium, arelatively recently synthesized compound, canfacilitate remineralization on the tooth. However,conventional experimental techniques can only
evaluate changes in quantitative factors such as
mineral content and hardness of the tooth; theycannot measure detailed changes in crystallizationthat determines the strength of the tooth. For
these latter purposes, we turned to X-ray
crystallographic studies.

Tooth crystals are eroded on scales of ~0.1 mm
in early-stage caries; therefore, measurement at
the micrometer (μm) level is required in order toexamine changes in the crystals. Such finemeasurements can only be achieved using X-ray
microbeams at SPring-8. To this end, early-stage
caries were experimentally generated on enamel
samples extracted from bovine teeth; thesesamples were then subjected to remineralization fora certain period of time in human oral cavities.
Remineralization was achieved through thechewing of gum that contained phosphoryl
oligosaccharides of calcium. Healthy, demineralized,
and remineralized areas were then analyzed using
X-ray microbeams.
This experiment revealed that demineralization
occurs at the crystal level but not at the atomic
level, the amount of crystals as well as mineralcontent in the remineralized area increases, andthe crystals are oriented in the same manner
found in a healthy tooth.

Publication: N. Yagi et al.; Journal of Synchrotron Radiation 16 (3), 398-404 (2009)
T. Tanaka et al.; Caries Research 44 (3), 253-259 (2010)

Tooth structure and early-stage caries
Healthy toothIn the early-stage caries, minerals inside the enamel
are eroded (demineralization) and the demineralized
area becomes cloudy compared to the surrounding
healthy area. At this stage, if phosphate and calcium
ions in saliva are supplied to the demineralized area,remineralization can be induced.

Tooth with early-stage caries

Phosphoryl oligosaccharides of calcium canfacilitate recovery from early-stage caries Enamel

Remineralized tooth

150 μmX-ray microbeam
EnamelEnamelEnamelDentinDentinDentinHealthy Tooth Dentin
Loss ofhydroxyapatite

Demonstration of recrystallization inducedby phosphoryl oligosaccharides of calcium
EnamelGums
Bone

Measured using conventionaltransversal microradiography
Mineral content decreases inthe demineralized area (red),
while it is restored in theremineralized area (blue).

Changes in crystallinity

90

Measured using X-ray
microbeams at SPring-880
7060504030
remineralized area

20

demineralized area

100100200

Depth from the surface (μm)

10300

Crystallinity of the demineralized
area (red) is degraded comparedto the healthy area (yellow),while crystallinity in theremineralized area (blue) isrestored.

1.2

Crystallinity (relative value)

Dental Pulp

Changes in mineral content
Mineral content (vol.%·μm)

Dentin10.8
0.60.4

healthy area0.2

remineralized area0

demineralized area-0.2-50050100150

200

250

Depth from the surface (μm)

300

The strength of tooth enamel is afunction of the arrangement of small
crystals(hydroxyapatite)
into
hexagonalcolumns
with
20-nanometer (nm) diameter and
100-nm length. This experiment
revealed that at the early stage ofcaries development, hydroxyapatite islost at the crystal level, leading to theformation of voids between crystals.
Moreover, remineralization promoted
by chewing gum containing
phosphoryl oligosaccharides ofcalcium fills these voids betweenhydroxyapatite crystals.

Tooth withearly-stage caries

Re-crystallized tooth

11