JPH0637379B2 - Topical for treatment of periodontal disease - Google Patents

Description

TECHNICAL FIELD OF THE INVENTION The present invention relates to oral compositions. More specifically, the present invention relates to an external preparation for the treatment of periodontal disease, which contains vitamin K ₂ and / or histidine hydrochloride, has an excellent vascular strengthening action, and is effective for the treatment of periodontal diseases such as gingivitis.

2. Description of the Related Art In recent years, with the advent of an aging society, the prevalence of periodontal disease has increased in Japan, and the establishment of treatment and prevention methods for it has been desired. Periodontal disease is said to start when plaque and tartar are accumulated in the gingival sulcus to stimulate the gingiva and cause gingivitis. Various chemical mediators such as serotonin, bradykinin, and prostaglandin are produced in the gingival tissue that is in an inflammatory state, and the gingival crevicular epithelium and the gingival capillary wall are weakened and cause increased permeability, which results in the gingival crevicular fluid. Various clinical symptoms such as increase, bleeding from the gingival mucosa, and deepening of the gingival sulcus appear. When such inflammation of the gingiva is further exacerbated, the periodontal tissue becomes weakened, which eventually causes destruction of the tissue, leading to alveolar pyorrhea.

Many treatments for such periodontal diseases are merely surgical therapy,
In addition, anti-inflammatory agents and antibacterial agents are only used as medicinal agents.

Problems to be Solved by the Invention As described above, the conventional medicinal agents used for periodontal disease are anti-inflammatory agents or antibacterial agents, and there is no agent for improving the weakened tissue itself, and treatment for the purpose. Has not been done.

In view of such circumstances, the present inventors have conducted earnest research on a drug that enhances resistance of the tissue to physical stimulation in order to improve weakened periodontal tissue, and as a result, vitamin K ₂ and histidine hydrochloride were locally applied. It was found that the administration of the drug has a remarkable effect on the treatment of periodontal disease, and the present invention has been completed.

Means for Solving the Problems That is, the present invention provides an external preparation for the treatment of periodontal disease, which comprises one or two active ingredients selected from the group consisting of vitamin K ₂ and histidine hydrochloride. It is provided.

Vitamin K ₂ contained in the oral composition of the present invention as an active ingredient is conventionally known as a hemostatic agent, while histidine hydrochloride is known as an ulcer tissue repair agent, but it has an action to enhance capillary resistance. Nothing is known about having. Furthermore, it was surprisingly found that the composition containing these drugs showed no effect by oral administration, but exhibited an effect only by local administration.

Examples of the dosage form of the composition of the present invention include toothpaste, powdered toothpaste, liquid toothpaste, mouthwash, ointment, cream, pasta, troche, chewing gum, patch and the like.

(A) Next, the results of testing the capillary action and mucolytic effect of the pharmacological agents (vitamin K ₂ and histidine hydrochloride) contained in the composition of the present invention are shown.

(I) Capillary-enhancing action (Test method) The abdomen of male wister rats (7-8 weeks old) was depilated, and an ointment containing a test drug efficacy compound in a base (Macrogol ointment, manufactured by Maruishi Pharmaceutical Co., Ltd.) was used. It was applied for a day. Application was for 5 hours per day, during which time it was covered with wrap and surgical tape. After the application, the skin of the application area is 300 mmHg using a purpura meter (made by Iwashiya) equipped with an absorption angle of 20 mm in diameter.
After suctioning for 60 seconds, the purple spots formed in a circle having a diameter of 10 mm were counted after 5 minutes. On the other hand, the control group was similarly coated with only the base material. Compare the results according to the following criteria,
Efficacy for vascular strengthening was evaluated.

(Evaluation Criteria) ++: Extremely effective ++: Effective ++: Effective ±: Slightly effective −: Ineffective Table 1 shows the results.

(Ii) Mucous membrane stripping action (Test method) Similar to (i) above, the mucous membrane stripping action was examined using an ointment containing a drug.

A golden hamster (male, body weight 100 to 116 g) was general anesthetized, an ointment was applied to the cheek pouch, left for 30 minutes, washed with 25 ml of distilled water, and left for 24 hours. After that, the cheek pouch tissue was removed, and a tissue sample was immediately prepared according to a conventional method. Observation by an optical microscope was made to be positive + if the mucosal exfoliation was observed, and negative − if it was not observed. The results are shown in Table 1.

Furthermore, the final evaluation of the drug was evaluated according to the following criteria in consideration of the results of the vascular strengthening action and the mucous membrane detaching action.

⊚: Very good ◯: Good x: Poor The results are shown in Table 1.

As is clear from Table 1, the amount of vitamin K ₂ added to the composition of the present invention as an active ingredient is 0.0001.
It is preferably from 10 to 10% by weight. Compounding amount is 0.000
If it is less than 1% by weight, preferable capillary resistance cannot be obtained, and a sufficient therapeutic effect cannot be obtained. On the other hand, the compounding amount is 10
If it exceeds 5% by weight, side effects such as mucous membrane detachment occur, which is not preferable.

For the same reason, the compounding amount of chlorine histidine is 0.
It is preferably 0001 to 10% by weight.

(B) Administration Method Furthermore, the following test was conducted to compare the specificity of the drug-inhibiting agents contained in the composition of the present invention with respect to the blood vessel-enhancing action due to the difference in administration method.

Wister male rats (7 to 8 weeks old) were used, and one group had the best overall result in the above test (A), containing vitamin K ₂ and histidine hydrochloride alone at 10% by weight, or 10% by weight each. The formulated macrogol ointment was applied in the same manner. In the other group, the medicinal agent was suspended in a 0.5% by weight CMC solution, and was orally administered once a day for 3 days in consideration of the same concentration of the medicinal agent locally. The blood vessel strengthening effect of each animal was evaluated by the number of purpura as in the test (A). The results are shown in Table 2.

As is clear from Table 2, the blood vessel-enhancing action of these drugs, whether alone or in combination, is effective only when administered locally.

Furthermore, as other components to be added to the composition of the present invention,
Appropriate known ingredients are used depending on the type of the external preparation for treating periodontal disease.

For example, for toothpaste, an abrasive such as dicalcium phosphate, calcium carbonate, calcium hydrogen phosphate; a binder such as sodium carboxymethyl cellulose, hydroxyethyl cellulose, carrageenan, polyvinyl alcohol, carboxy vinyl polymer; glycerin, sorbitol, propylene glycol. Wetting agents such as polyethylene glycol and 1,3-butylene glycol; effervescent agents such as sodium lauryl sulfate and auroyl sarcosine sodium; flavoring agents such as essential oils such as peppermint and spearmint; flavoring agents such as menthol; sweetening agents such as saccharin sodium; In addition, a preservative is appropriately mixed.

It manufactures according to a conventional method using these components.

Also, powder toothpaste, liquid toothpaste, mouthwash, ointment, cream,
Pasta, troche, chewing gum, patch and the like are also prepared by blending the ingredients according to the properties of the product according to a conventional method.

The patch is an intraoral preparation consisting of a film-like adherent which is applied to the moist mucous membrane of the oral cavity and has excellent adhesiveness, which prevents the outflow of the administered drug and protects the damaged portion of the mucous membrane in the oral cavity. is there. As an example of the patch, a water-soluble polymer substance having adhesiveness to mucous membrane, for example, hydroxypropyl cellulose, carboxyvinyl polymer or the like, which is formed into a film, can be mentioned.

The external preparation for treating periodontal disease of the present invention may further contain various medicinal agents. For example, antibacterial agents such as chlorhexidine, tetracycline, minocycline, iodine, acrinol, hinokitiol, penicillin; lysozyme,
Anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (indomethacin, ibuprofen, flurbiprofen, ketoprofen, pranoprofen, aspirin, sodium salicylate), glycyrrhizinate, azulene, glycyrrhizin; tranexamic acid, ε-aminocaproic acid, carbazochrome, Hemostatic agents such as adrenochrome and bioflavonoids; blood flow improving agents such as vitamin E derivatives (eg vitamin E nicotinate); analgesics such as camphor, eugenol, phenol, procaine; tooth strengthening agents such as various fluorine compounds, Examples include plaque formation inhibitors such as dextranase and mutanase.

Example Next, the external preparation for treatment of periodontal disease of the present invention will be described more concretely with reference to Examples.

Example 1 (Toothpaste) A toothpaste having the following composition was produced by a conventional method.

Examples 2 to 3 (toothpaste) Toothpaste was produced in the same manner as in Example 1 except that the following medicinal agents were added instead of vitamin K ₂ .

Example 4 (Toothpaste) A toothpaste was produced in the same manner as in Example 1 with the following composition.

Example 5 (powder toothpaste) A powder toothpaste having the following composition was produced according to a conventional method.

Example 6 (Chewing gum) A chewing gum having the following composition was produced by a conventional method.

Example 7 (Mouthwash) A mouthwash having the following composition was produced by a conventional method.

Example 8 (troche) A troche was produced according to a conventional method with the following composition.

Example 9 (gingival massage cream) A gingival massage cream was produced according to a conventional method with the following composition.

Example 10 (Tablet for mouthwash) A tablet for mouthwash was produced according to a conventional method with the following composition.

Example 11 (Oral Pasta) An oral pasta was produced according to a conventional method with the following composition.

Example 12 (Ointment-shaped oral preparation) An ointment-shaped oral preparation was made according to a conventional method with the following composition.

EFFECTS OF THE INVENTION (Examples of Use) Example 1 above except that the compounding amounts of the medicinal agents were as follows.
Using the oral pasta produced in the same manner as in Example 1, the effect of improving gingivitis was tested by the following method. Test subjects: 28 men (22 to 3) with inflammatory changes in gingiva
0 year old) and 12 women (18 to 25 years old) were selected and divided into 4 groups of 10 people so that the inflammation symptoms were almost the same.

Test method: The above 4 groups were designated as A to D groups, and oral pasta according to the following formulation was given.

Group A Oral pasta with 1% vitamin K ₂ Group B Oral pasta with 1% histidine hydrochloride Group C Oral pasta with 1% vitamin K _{2 and} 1% histidine hydrochloride D group Control: Oral pasta base Only, the same drug-free subject was given the same new toothbrush and the gingiva was massaged for 4 weeks after each meal. Brushing method was free.

Judgment of improvement effect on gingivitis: The PMA Index evaluated. That is, a score of 1 (present) or 0 (absent) is given depending on the presence or absence of inflammation of the anterior papilla (P), the marginal gingiva (M), and the attached gingiva (A), and the total score is the index of each patient And The scores of each patient before and after the test were compared, and the improvement rate was calculated by the following formula.

The results are shown in Table 4.

As is clear from Table 4, all of the A, B and C groups have a significant improving effect on the D group (control).

The external preparation for the treatment of periodontal disease of the present invention shows a vascular strengthening effect to improve the weakened periodontal tissue, enhances the resistance of the tissue to physical stimulation, and treats periodontal diseases such as gingivitis, etc. A remarkable effect is recognized in.

Continuation of front page (56) Reference JP-A-57-171909 (JP, A) JP-A-61-15818 (JP, A) JP-A-60-25918 (JP, A) JP-A-62-201825 (JP , A)

Claims (3)

[Claims] 1. An external preparation for treatment of periodontal disease, which comprises one or two active ingredients selected from the group consisting of vitamin K ₂ and histidine hydrochloride. 2. A vitamin K ₂ content of 0.0001 to 1
The external preparation for treatment of periodontal disease according to the above (1), which is 0% by weight. 3. The histidine hydrochloride content of 0.0001-
The external preparation for treatment of periodontal disease according to item (1), which is 10% by weight.