JPH0761933B2 - Oral composition - Google Patents

Description

TECHNICAL FIELD OF THE INVENTION The present invention relates to oral compositions. More specifically, the present invention relates to an oral composition containing an extract of Hypericum perforatum and / or an extract of Lentinus edodes, which has an excellent vascular strengthening action and is effective for the prevention and 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 the inflammation of the gingiva further deteriorates, 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, antiphlogistics 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 diligent research on a drug that enhances resistance to physical irritation of tissue in order to improve weakened periodontal tissue, and as a result, Hypericum perforatum extract and shiitake extract are locally applied. It was found that the administration of the drug has a significant effect on the prevention and treatment of periodontal disease, and the present invention has been completed.

Means for Solving the Problems That is, the present invention is one selected from the group consisting of lower alcohols of Hypericum perforatum, hydrous lower alcohols or water extracts, and shiitake lower alcohols, hydrous lower alcohols or water extracts. Alternatively, the present invention provides a composition for oral cavity containing two kinds of extracts.

Hypericum perforatum, which is a raw material in the oral composition of the present invention, is conventionally known to contain a component having a hemostatic action, while the bacterium of Shiitake mushroom contains a component having an anti-ulcer action and the like. However, nothing is known about the inclusion of a component that enhances capillary resistance. Furthermore, it was surprisingly found that the composition containing these extracts had no effect by oral administration, but exhibited an effect only by local administration.

Extraction of the extract compounded in the oral composition of the present invention may be carried out by a known ordinary method.

As the solvent used for the extraction, methanol, ethanol, a lower alcohol such as isopropanol, or water,
Alternatively, a mixture of the lower alcohol and water is used.

The amount of the solvent used is 1 to 60 parts by weight, preferably 5 to 30 times the amount of the substance to be extracted. Extraction temperature is room temperature ~ 11
It may be 0 ° C., but it is convenient to carry out at around the boiling point of the extraction solvent.

The following is a specific example of the extraction procedure. (A) Hypericum extract Hypericum erectum, Thunb. 1 kg of whole plant
Minced and add 90% ethanol 8 to it. This is heated to 60 to 70 ° C for extraction, and then filtered. The residue is extracted again with 90% ethanol 8. The same extraction operation is performed 4 times in total, and all the extract solutions are combined. After concentrating this under reduced pressure at 40 ° C, adjust the concentration of the concentrated liquid by adding JP purified water so that the ethanol content becomes 70%. Further, it is left to stand at room temperature for 5 to 7 days for aging. Then, this is filtered, the filtrate is concentrated under reduced pressure, and ethanol (JP) and purified water are added to the concentrate to adjust the ethanol concentration to 50% and the total amount to about 10. Furthermore, it is left to stand in a cold place for 7 to 10 days for aging, and then filtered, and 50% ethanol is added to the filtrate to obtain Extract 10. The extract is dried under reduced pressure to obtain a Hypericum perforatum extract.

(B) Shiitake Extract To obtain the shiitake extract, the shiitake (Cortinellus sh
(iitake, P. Henn.) 10 kg of dried product is chopped, 70% ethanol 50 is added, and the mixture is immersed at room temperature for about 2 weeks and then filtered. The residue was extracted with 50% ethanol 50 times twice in the same manner, all the extracts were combined, concentrated under reduced pressure on a water bath, and ethanol and purified water were added to the concentrate to adjust the alcohol concentration to 50%.
%, Adjust the total amount to about 50. This is left to stand in a cold place for 7 to 10 days for aging and then filtered, and 50% ethanol is added to the filtrate to obtain an extract 50. The extract is dried under reduced pressure to obtain a shiitake extract.

For Hypericum perforatum and Shiitake mushroom, any of lower alcohols other than ethanol, water, or a mixture of lower alcohol and water at various ratios can be used to obtain an extract by the same operation.

Examples of dosage forms of the composition of the present invention containing such an extract include toothpaste, powdered toothpaste, liquid toothpaste, mouthwash, ointment, cream, pasta, troche, chewing gum, and patch.

(A) Next, capillaries of Hypericum perforatum extract (above (a) 90% ethanol extract) and shiitake extract (above (b) 70% ethanol extract), which are medicinal agents to be added to the composition of the present invention. The result of having tested the strengthening effect and the mucous membrane exfoliation effect is shown.

(I) Capillary-enhancing action (Test method) The abdomen of Wistar male rats (7-8 weeks old) was shaved, and an ointment was prepared by adding a test drug efficacy to a base (Macrogol ointment, manufactured by Maruishi Pharmaceutical Co., Ltd.). It was applied for 3 days. 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 applied part was sucked at 300 mmHg for 60 seconds using a purpura meter (made by Iwashiya) equipped with an absorption angle of 20 mm in diameter, and after 5 minutes, the purpura formed in a circle with a diameter of 10 mm was counted. . On the other hand, the control group was similarly coated with only the base material. The results were compared according to the following criteria, and the effectiveness of the blood vessel strengthening effect was evaluated.

(Evaluation Criteria) +++: Extremely Effective +++: Effective +: Effective ±: Fairly 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.

25ml of golden hamster (male, weight 100-116g) was anesthetized under general anesthesia and ointment was applied to the cheek pouch and left for 30 minutes.
It was washed with distilled water and left for 24 hours. Then, the buccal pouch tissue was removed, and a tissue sample was immediately prepared according to a conventional method, and observed by an optical microscope to show histologically mucous membrane delamination as positive +, and as not negative, as negative. 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 Hypericum perforatum extract contained in the composition of the present invention as an active ingredient is 0.001.
It is preferably about 10% by weight. 0.001% by weight
When it is less than the above range, preferable capillary resistance cannot be obtained, and sufficient preventive and therapeutic effects cannot be obtained. On the other hand, if the blending amount exceeds 10% by weight, side effects such as mucous membrane peeling occur, which is not preferable.

For the same reason, the compounding amount of shiitake extract is 0.00
It is preferably from 1 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.

Wistar male rats (7 to 8 weeks old) were used, and one group had the best overall results in the test (A), and the extract of Hypericum perforatum and Lentinus edodes alone was mixed at 1010% by weight or each 10% by weight. A macrogol ointment containing the same was applied in the same manner. In addition, the other group had 0.5 medicinal properties.
It was suspended in a wt% CMC solution and orally administered once a day for 3 days, taking into consideration that the concentration of the local drug was the same.
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 components are used depending on the type of the oral composition.

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; foaming agents such as sodium lauryl sulfate and sodium lauroyl sarcosine; essential oils such as peppermint and spearmint; flavoring agents such as menthol; sweeteners such as saccharin sodium; A preservative is appropriately mixed.

It manufactures according to a conventional method using these components.

Also, 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 oral composition of the present invention may further contain various medicinal agents. For example, antibacterial agents such as chlorhexidine, tetracycline, minocycline, iodine, acrinol, hinokitiol, penicillin; lysozyme, nonsteroidal anti-inflammatory agents (indomethacin, ibuprofen,
Anti-inflammatory agents such as flurbiprofen, ketoprofen, pranoprofen, aspirin, sodium salicylate), glycyrrhizinate, azulene, glycyrrhetinic acid;
Astringents such as salt, aluminum allantoinate, tannic acid; tranexamic acid, ε-aminocaproic acid,
Hemostatic agents such as carbazochrome, adrenochrome and bioflavonoids; blood flow improving agents such as vitamin E derivatives (eg vitamin E nicotinate); root canal anti-inflammatory agents such as camphor, eugenol and phenol; local anesthetics such as procaine; various fluorine compounds, etc. Examples thereof include dental plaque formation inhibitors such as dentin strengthening agents, dextranase, and mutanase.

Example Next, the composition for oral cavity of the present invention will be described more specifically by way of examples. In the following examples, Hypericum perforatum extract and Shiitake extract of the above (a) and (b) were used, but not limited to this, it can be obtained by extraction with lower alcohol, water, or a mixture thereof. It may be an extract.

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

Examples 2 to 3 (toothpaste) A toothpaste was produced in the same manner as in Example 1 except that the following medicinal agents were added instead of the Hypericum perforatum extract.

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. Ingredient content (% by weight) Gum base 65.0 Mannitol 20.0 Sorbit 3.5 Fragrance 1.5 Shiitake extract 10.0 Total 100 Example 7 (mouse wash) A mouse wash was prepared according to the following composition.

Example 8 (troche) A troche was produced according to a conventional method with the following composition. Composition (wt%) Gum arabic 6.0 Fructose 20.0 Glucose 20.0 Maltose 30.0 Fragrance 1.0 Hypericum extract 0.001 Water remaining total 100 Example 9 (gingiva massage cream) A gingival massage cream is produced according to the following method according to the conventional method. did. Ingredient content (% by weight) White petrolatum 8.0 Stearyl alcohol 6.0 Propylene glycol 4.0 Polyethylene glycol 2000 25.0 Polyethylene glycol 400 37.0 Cetyl alcohol 7.0 Hypericum perforatum extract 8.0 Shiitake extract 0.001 Water balance 100 Total Example 10 (gargling tablet) An irrigation tablet was produced according to a conventional method with the composition of. Ingredients Content (wt%) Sodium hydrogen carbonate 55.0 Dibasic sodium phosphate 15.0 Polyethylene glycol 6000 3.0 Citric acid 12.0 Ethanol 6.0 Fragrance 4.0 Hypericum extract 5.0 Total 100 Example 11 (oral pasta) Oral pasta was produced according to the method.

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

EFFECTS OF THE INVENTION (Example of Use) The same as Example 11 except that the compounding amounts of the drug agents were as follows.
Using the oral pasta produced in the same manner as above, the effect of improving gingivitis was tested by the following method. Test subjects: 28 males (24 to 33 years old) with gingival inflammatory changes
And 12 females (21-26 years old) were selected and divided into 4 groups of 10 females 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% Hypericum extract (90% ethanol extract) Group B Oral pasta with Shiitake extract (70% ethanol extract) 1% Group C Oral pasta with Hypericum extract (Above 90% ethanol extract) 1% and shiitake extract (above 70% ethanol extract) 1
% Group D control: oral pasta base only, no drug combination The subject was given the same new toothbrush and after each meal the gingiva was massaged for 4 weeks. Brushing method was free.

Judgment of improvement effect on gingivitis: Evaluated by PMA Index. 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 composition for oral cavity of the present invention improves fragile periodontal tissue showing a vascular strengthening action, enhances resistance to physical stimulation of the tissue, and prevents and treats periodontal diseases such as gingivitis. Remarkably effective.

Claims (3)

[Claims] 1. Containing one or two kinds of extracts selected from the group consisting of lower alcohol of Hypericum perforatum, hydrous lower alcohol or water extract, and lower alcohol of Shiitake mushroom, hydrous lower alcohol or water extract. A composition for oral cavity, comprising: 2. The content of Hypericum perforatum extract is 0.001-10.
The composition for oral cavity according to the above (1), which is in a weight percentage. 3. The oral composition according to item (1), wherein the shiitake extract content is 0.001 to 10% by weight.