JPS59206304A - Tooth treatment composition - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to dental care and oral hygiene compositions that have anti-collagenolytic activity and are therefore useful in preventing or curing caries.

Cavity is an infectious disease that occurs as a result of the progressive breakdown of both inorganic and organic substances in teeth. The progression of caries begins with the interaction between microorganisms attached to the tooth surface and carbohydrates in contact with the susceptible tooth surface. Cavity damage begins on the external surface of permanently erupting tooth enamel or the exposed cementum of the tooth root surface and then progresses centripetally deep into the dentin. As mentioned above, decay begins with the fermentation of carbohydrates by microorganisms that produce acids that cause localized demineralization of tooth tissue. Therefore, the breakdown of hard tissues such as enamel, dentin, cementum or bone,
It begins with the dissolution of inorganic substances in these tissues, such as hydroxyapatite. As a result of tissue breakdown, decomposition of the organic matrix also occurs, since in mature enamel only 2% of the total composition of the enamel contains the hydroxyapatite. The case of enamel is different from that of other hard tissues (dentin, cementum fenestrae, and bone). It consists of a highly cross-linked collagen matrix that resists disintegration under the influence of chemical agents.

Natural collagen resists normal proteolytic digestion (eg, by proteolytic enzymes such as trypsin and chymotrypsin) under physiological conditions due to its triple polypeptide helical structure. However, collagen can be cleaved into two large fragments by collagenases within the tissue and then further cleaved by non-specific peptidases.

The present inventors have recently discovered that dentin material extracted from both carious human teeth and healthy human teeth has collagenolytic activity, and the activity is particularly high in carious teeth. Ta. The above facts point out that during tooth development, in addition to collagen, an inactive form of collagenase is produced, which can be activated during the progression of caries and thus disrupt the collagen matrix of the dentin. It is. Thus, in fact, the complete collagen-degrading activity in the progression of caries disease is due to the dentin itself, although it is known that certain bacteria involved during the progression of caries can secrete their own collagenase enzymes. Derived from collagenase.

The present inventors have carried out extensive research in view of the above-mentioned circumstances, and have found that the collagen-degrading activity of the dentin of caries has a thiol group in a free form (such as cysteine) or in a latent form such as disulfide. , either in the form of metal salts of the thio group, and that cysteine was inhibited or completely suppressed in vivo in rats fed a cariogenic sugar diet. It was discovered that the progress of damage to dentin due to caries is inhibited, and the present invention was completed.

That is, the present invention provides compounds selected from non-toxic compounds 8 having a thiol group in free form, a pharmacologically acceptable thiol group or a thiol group in the form of a complex, and non-toxic compounds having a disulfide group. containing an effective amount of at least one collagenase inhibitor;
A dental care composition for preventing or curing the formation of cavities is provided containing a pharmacologically acceptable carrier to be applied to and maintained in contact with the tooth.

According to the invention, active collagenase inhibitors include sycotoxic aliphatic and aromatic monothiol compounds, S-toxic aliphatic- and aromatic polythiol compounds, and pharmacologically compatible thiol groups in said compounds. It can be selected from salts and complexes with cations (eg alkali metal salts, alkaline earth metal groups, etc.).

Furthermore, according to the invention, aliphatic or aromatic disulfides are used as collagenase inhibitors, in which case the compositions of the invention contain the disulfide groups in order to generate a pair of free thiol groups in situ. Optionally contain a suitable non-toxic reducing agent. Alternatively, the disulfide compound and the supplementary formulation with the appropriate reducing agent may be applied separately to the tooth in any order.

Further active compounds suitable according to the invention for use as collagenase inhibitors include any edible substances or other pharmacologically acceptable substances containing thiol or disulfide compounds as a prosthetic group. It is a substance. Such substances include egg yolk,
Examples include protein and hair protein inducers and protein derivatives such as extracts of garlic, onion, green onion, chive, shallot and the like.

A preferred collagenase inhibitor for use according to the invention is cysteine.

The compositions of the invention preferably further contain a pharmacologically acceptable antioxidant, such as vitamin C, especially if the compositions contain free thiol groups as active ingredients.

The novel compositions of the present invention are adapted for both personal daily oral hygiene and dental practice as toothpastes (e.g. toothpastes, mouthwashes, tooth powders, etc.) and medicated chewing gums.

The main applications of the composition of the present invention in dentistry are the sub-inner layer and inner layer of fi+ tooth cavities, (2) preparation of tooth cavities with the composition (3) indirect tooth M-covering method, (4) filling of root canals; (5) application to any natural abutment tooth before cementation of a pontic; (6) application to resorption areas of bone, cementum or dentin; (7) oral surgery. This includes rinsing the mouth after periodontal treatment, including periodontal treatment.

Adapted and specific use of the compositions of the present invention determines various parameters of the compositions, namely the nature and concentration of the active collagenase inhibitor, the chemical and physical properties of the carrier, and compositions of the type in question. The proper selection is determined, such as the nature of any other additives present selected from additives conventionally used in the process.

Therefore, when the composition of the present invention is used as a toothpaste, the composition contains active collagenase inhibitors manufactured by M.
About 1 to 2000 milliequivalents of free thiol tea leaves or latent thiol groups per liter, preferably about 100
It should be contained in a concentration corresponding to ~1000 milliequivalents. Thus, for example, when cysteine is used according to the invention as an active inhibitor in a liquid toothpaste, a suitable concentration is 0.1 mol/liter, which corresponds to about 1.6 Wjffi%.

When the composition of the present invention is used as a toothpaste, the composition may be used in powder, ointment, or liquid form. In addition to the collagenase inhibitor according to the invention, the toothpaste also contains various substances commonly used in the past. So, for example, in toothpaste, calcium carbonate,
dicalcium phosphate (dicalcium p
Abrasives and brighteners such as phosphat, calcium phosphate, calcium sulfate, silica in patterned form, etc., surfactants such as sodium lauryl sulfate, sodium dodecylbenzene sulfonate, etc., natural rubber, synthetic gums, gummy substances (e.g. gelling agents (or thickening agents) such as carboxymethylcellulose, tragacanth, guar, starch, etc.), saccharin, aromatic oils (e.g. spearmint oil, peppermint oil, oil of cornstarch), etc. flavoring agents and/or natural or synthetic sweeteners, other coloring agents, whitening agents (e.g. titanium dioxide, preservatives (e.g. sodium benzoate), emulsifiers, acidifying agents (e.g. phosphoric acid, citric acid) ) and other excipients are mixed in.

The compositions of the present invention can be prepared in the form of powders or toothpastes by conventional methods of mixing the components either in the dry state or as a slurry or solution.

Generally, according to the present invention, the liquid in the toothpaste or mouthwash primarily includes water, glycerol, sorbitol, propylene glycol, 8, and appropriate mixtures thereof. A mixture of water and glycerol is preferably used, perhaps in conjunction with sorbitol.

The present invention will be explained in more detail below based on composition examples, but the present invention is not limited only to these examples.

Example 1 (Toothpaste) Paraffin 15%, PA
B-ester 0.2
%, methylcellulose
1.8%, aromatics 2
%, cysteine 1.5%
, Distilled water Remaining amount Example 2 (Toothpaste) Calcium carbonate 50
%, tricalcium phosphate
5% glycerol
20%, tragacanth
2% aromatics
0.8%, cysteine 2
%, PAB-ester 0.1
% Distilled water Remaining Example 3 (Toothpaste) Aluminum hydroxide 40%,
Sodium fluoride 0.1%, sorbitol (70% solution) 25%, glycerol 5%, aromatics
1.2%, sodium alginate
1% PAB-ester o, i% saccharin
0.25%, cysteine
2%, permanent
Long amount Example 4 (Toothpaste) Cystine 3%, aromatic substances 29, sodium cyclamate (Na-cyclaITIate)
0.5%, cleaning agent (Texapon)
pon), L 100) 1
% Calcium phosphate remaining amount Example 5 (mouth detergent methyl cellulose (low viscosity) 1
%, aromatic substances 1%
, PAB-ester 0.15%,
Citric acid (monohydrate) 1.0%, cysteine 2%, distilled water Remaining amount Example 6 (Toothpaste) Sodium cyclamate 0.
75%, aromatics 2.25
%, Cystine 6%, Tricalcium phosphate Residual Example 7 (Toothpaste) Aromatic substances 1%, Sodium fluoride 0.1%, Cleaning agent
1% cysteine
2%, saccharin sodium
0.25%, Microcrystalline Aluminum Hydroxide Residual Amount Example 8 (Jetstream Tooth Cleaning Agent) Conventional device for injecting a water stream at high speed. It was prepared using

Claims (1)

[Scope of Claims] 1. Non-toxic compounds having a thiol group in free form, a thiol group in a pharmaceutically acceptable salt or a thiol group in the form of a complex, and non-toxic compounds having a disulfide group. forming a cavity containing an effective amount of at least one collagenase inhibitor selected from among the compounds and a pharmacologically acceptable carrier to be applied to and maintained in contact with the tooth; A tooth care composition for prevention or treatment. 2. The tooth care composition according to claim 1, which contains a non-toxic aliphatic thiol or aromatic thiol as the collagenase inhibitor. 3. Vitamins. 4. The tooth care composition according to claim 2, which further contains C. 4. The tooth care composition according to claim 1, which contains a nontoxic aliphatic disulfide or aromatic disulfide as the collagenase inhibitor. 6. A dental care composition according to claim 4, further comprising a non-toxic reducing agent capable of reducing the disulfide groups to yield 51 pairs of thiol groups. A tooth care composition according to claim 2 or claim 6, which contains cysteine as said collagenase inhibitor. The tooth care composition according to claim 1, 2, 6, 4, 5 or 6, which contains a collagenase inhibitor.8 Free thiol group or potential thiol. A dental care composition according to claim 6, containing an amount of collagenase inhibitor corresponding to 100 to 1000 milliequivalents per liter. Claims 1, 2, 3, 4, 5 associated with use as a toothpaste in
The tooth care composition according to item 6, 7 or 8.