JP2607945B2 - Periodontal tissue repair promoting composition - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an oral composition which is excellent in promoting periodontal tissue repair and is effective in treating periodontal disease.

(Prior art and problems) Periodontal disease is two major diseases of dentistry along with dental caries. With the advent of an aging society in recent years, the prevalence of periodontal disease in Japan has increased remarkably. Establishment of treatment and prevention methods is desired.

However, at present, treatment for such periodontal diseases relies on mere surgery, and even in the case of medicinal agents,
Only antiphlogistics and antibacterials are used, and there are no drugs that improve the tissue itself that is vulnerable to periodontal disease.
There is no treatment for this purpose.

(Means for Solving the Problems) In view of such circumstances, the present inventors have conducted intensive studies on compounds that promote tissue repair in order to improve weakened periodontal tissue. As a result, the present invention provides a composition for promoting periodontal tissue repair, which comprises tinoridine hydrochloride and / or tiaramid hydrochloride.

Periodontal disease is thought to occur because plaque and tartar accumulate in the gingival sulcus to stimulate the gums and cause inflammation. Various chemical mediators such as serotonin, bradykinin, and prostaglandin are produced in the gingival tissue that has fallen into an inflammatory state, which weakens the gingival sulcus epithelium and the gingival capillary wall, causing hyperpermeability, etc. Various clinical symptoms such as an increase in fluid, bleeding from the gingival mucosa, and deepening of the gingival sulcus appear. When such gingival inflammation further worsens, the periodontal tissue becomes weak and eventually destroys the tissue.

The oral composition of the present invention is very effective in repairing weakened periodontal tissue.

Compounds used in the present invention include tinolidine hydrochloride and tiaramid hydrochloride. Conventionally, tinolidine hydrochloride and tiaramid hydrochloride have been used orally as anti-inflammatory and analgesic agents, but are not known to have a tissue repair-promoting action by local administration. The compounding amount of the present compound is 0.001 to the total amount of the composition.
5% by weight is preferred. When the amount is less than 0.001% by weight, the effect of promoting tissue repair cannot be said to be sufficient. On the other hand, when the amount is more than 5% by weight, problems such as irritation to the oral mucosa occur.

The composition of the present invention may further contain various medicinal agents. For example, chlorhexidine, iodine,
Antibacterial agents such as acrinol and hinokitiol; antibiotics such as tetracycline and minocycline; anti-inflammatory agents such as lysozyme chloride, glycyrrhizinate, azulene and purple root extract; astringents such as sodium chloride, aluminum allantoinate and tannic acid; tranexamic acid; ε-
Aminocaproic acid, carbazochrome, adrenochrome,
Examples include hemostatic agents such as bioflavonoids, blood flow improvers such as vitamin E nicotinate, dentin enhancers such as fluorine compounds, and bad breath suppressants such as sodium copper chlorophin and flavonoids.

Further, other components to be added to the composition of the present invention can be appropriately selected within a range that does not impair the performance according to the type of the composition. For example, abrasives such as calcium carbonate, dibasic calcium phosphate, aluminum hydroxide, and silica; binders such as sodium carboxymethylcellulose, hydroxyethylcellulose, carrageenan, polyvinyl alcohol, and carboxyvinyl polymer; glycerin, sorbitol, propylene glycol, and polyethylene glycol , Humectants such as 1,3-butylene glycol, foaming agents such as sodium lauryl sulfate, sodium lauroyl sarcosine, sweeteners such as saccharin sodium, palatinose, peppermint, spearmint,
Flavors such as anise, coloring agents, preservatives and the like can be mentioned.

This composition can be made into a dosage form such as a toothpaste, a toothpaste, a mouthwash, an ointment, a cream, a gel, a troche, a patch and the like by a conventional method. The patch is a film-like preparation that has excellent adhesive properties when applied to the wet mucous membrane in the oral cavity, prevents outflow of the administered drug, and protects the wound from covering. As an example of the patch, a water-soluble polymer substance having an adhesive property to the oral mucosa, for example, a product obtained by forming a hydroxypropylcellulose, a carboxyvinyl polymer, or the like into a film may be used.

(Effects of the Invention) Next, the compound used in the present invention was mixed with macrogol ointment to test the effect of promoting tissue repair.

Test-1 The test was performed with three Wistar rats per group.
Under ether anesthesia, the hair on the back is clipped with a clipper,
The back skin was disinfected with 70% ethanol. The back skin was gently pinched and stretched, and a 15 mm blade from the midline was punched out with a 15 mm long woodworking chisel, creating two wounds at the same time.

Immediately at the center of the wound, suture the center, apply about 500 mg of ointment per wound once a day for 5 days, remove the thread on the 4th day, kill the animal on the 6th day, and peel off the back skin The wound was cut into a strip having a width of about 8 mm using a scalpel. Using a rheometer, the tension (wound resistance) required for the wound to rupture was measured.

The results were shown as a mean ± standard deviation and a ratio of wound tension (g). The ratio is the ratio of the wound tension of the medicinal agent when the macro tension ointment containing no medicinal agent (control) is set to 100, and the higher the value, the better the tissue repair effect. To indicate that Table 1 shows the results.

As is clear from Table 1, all the compounds used in the present invention have a tissue repair promoting action. However, among other anti-inflammatory drugs, the steroidal anti-inflammatory drug hydrocortisone delayed tissue repair, and the non-steroidal acidic anti-inflammatory drug indomethacin did not affect tissue repair.

Test-2 Next, the gingivitis ameliorating effect was tested using a gingival massage cream prepared according to the following formulation.

Ingredients Blended amount (wt%) White petrolatum 10.0 Stearyl alcohol 6.0 Propylene glycol 4.0 Polyethylene glycol 2000 25.0 Polyethylene glycol 400 37.0 Cetanol 7.0 Methyl parahydroxybenzoate 0.1 Butyl paraoxybenzoate 0.1 Perfume 0.7 Water balance Total 100 test methods 28 men and 12 women with inflammatory changes in the gingiva were divided into 4 groups of 10 each so that the inflammatory symptoms were almost the same, and each group was given the gingival massage cream shown below. Used.

Group A: Gingival massage cream (control) Group B: Tinolizine hydrochloride 1% blended with gingival massage cream Group C: Gum massage cream blended with 1% tiaramid hydrochloride 1 day after regular brushing after meals 3 times a day About 0.5 g of the massage cream was applied to the fingers and massaged on the gums. The test period was 14 days, and gingival inflammatory symptoms were evaluated by the PMA Index. That is, a score of 1 (presence) or 0 (absence) is given based on the presence or absence of inflammation of the papillary gingiva (P), marginal gingiva (M), and attached gingiva (A) in the anterior teeth, and the total score is assigned to each patient's score. Index. Compare the scores of each patient before and after the test,
The gingivitis improvement rate was calculated by the following equation. Table 2 shows the results.

As is clear from Table 2, it can be seen that all the groups B, C and D show a significant improvement effect on the group A (control).

Next, the oral composition of the present invention will be described in more detail with reference to examples.

Example 1 (Toothpaste) According to the following composition, toothpaste was produced by a conventional method.

Ingredients Amount (% by weight) Calcium carbonate 45.0 Sodium carboxymethylcellulose 1.0 Glycerin 20.0 Sodium lauryl sulfate 1.5 Fragrance 1.0 Sodium saccharin 0.1 Tinolidine hydrochloride 1.0 Water balance Example 2 (troche) A troche was produced according to the following composition by a conventional method.

Ingredients Amount (% by weight) Arabic gum 6.0 Fructose 20.0 Glucose 20.0 Maltose 3.0 Flavor 0.1 Tiaramid hydrochloride 0.01 Water Remainder Total 100 Example 3 (Gingival Massage Cream) A gingival massage cream was manufactured according to the following composition by a conventional method.

Ingredients Blended amount (wt%) White petrolatum 10.0 Stearyl alcohol 6.0 Propylene glycol 4.0 Polyethylene glycol 2000 25.0 Polyethylene glycol 400 37.0 Cetanol 7.0 Methyl parahydroxybenzoate 0.1 Butyl paraoxybenzoate 0.1 Fragrance 0.7 Tinolidine hydrochloride 2.5 Water balance Total 100 Example 4 (Ointment) A gel was produced by a conventional method according to the following composition.

Ingredients Amount (% by weight) Hydroxyethylcellulose 4.0 Triacetin 12.0 Eudragit RS 2.0 Tinolidine hydrochloride 1.0 Glycerin Remainder Total 100

Claims (1)

(57) [Claims] 1. A composition for promoting periodontal tissue repair, comprising 0.001 to 5% by weight of tinolidine hydrochloride and / or tiaramid hydrochloride.