JPH09291018A - Composition for oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition for oral cavity, excellent in blood vessel- reinforcing action and effective in preventing and treating periodontal diseases such as gingivitis. SOLUTION: This composition for oral cavity is obtained by blending sap of a plant belonging to the genus Betula of the family Betulaceae. Further, the composition for oral cavity capable of moreover improving the effect is obtained by adding one or more kinds of components selected from lysozyme, a nonsteroidal antiinflammatory agent, dipotassium glycyrrhizinate, β- glycyrrhizin, ε-aminocaproic acid and sodium azulenesulfonate to the sap.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an oral composition. More specifically, the present invention relates to a composition for the oral cavity which contains sap of a birch plant of the family Birchaceae, has an excellent vascular strengthening effect, and is effective for the prevention and treatment of periodontal diseases such as gingivitis.

[0002]

2. Description of the Related Art In recent years, with the advent of an aging society, the morbidity of periodontal diseases has increased in Japan, and the establishment of a treatment and preventive method for this has been desired. Periodontal disease is said to begin when plaque and tartar accumulate in the gingival sulcus, stimulating the gingiva and causing gingivitis. Various chemical mediators such as serotonin, bradykinin, and prostaglandin are produced in gingival tissues that are in an inflammatory state, and the gingival crevicular epithelium and gingival capillaries become weakened, causing increased permeability, etc., resulting in an increase in gingival crevicular fluid. , Various clinical symptoms such as 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 treatments, and antiphlogistics and antibacterial agents are only used as medicinal agents.

[0003]

As described above, the conventional medicinal agents used for periodontal diseases are antiphlogistics or antibacterial agents, and there is no agent for improving the fragile tissue itself. No treatment is given.

[0004]

In view of such circumstances, the present inventors have conducted earnest research on a drug that enhances resistance to physical stimulation of tissue in order to improve weakened periodontal tissue, and as a result, The present inventor has completed the present invention, knowing that the sap of the birch plant of the family Birchaceae has a significant effect on the prevention and treatment of periodontal diseases. Of the birch family Birch genus used for folk remedies such as constipation, tonsillitis, cough and sore throat, fever, rheumatism, burn inflammation, hypertension, diuresis, gout etc. in Europe, China, Korea, Japan etc. Sap is not known to strengthen capillaries. Furthermore, it was surprisingly found that a composition containing sap of a birch plant of the family Birchaceae has no effect by oral administration, but exhibits an effect only by local administration.

In addition, the sap and lysozyme of the birch plant of the family Birchaceae, non-steroidal anti-inflammatory agents (indomethacin, ibuprofen, flurbiprofen, ketoprofen, planoprafen, aspirin, sodium salicylate), dipotassium glycyrrhizinate, β-glycyrrhizin. , A combination of at least one component selected from anti-inflammatory agents such as .epsilon.-aminocaproic acid and sodium azulene sulfonate was locally administered, and markedly effective in preventing and treating periodontal disease.

That is, the present invention is based on the sap of a birch plant of the family Birchaceae or lysozyme, a nonsteroidal anti-inflammatory drug (indomethacin, ibuprofen, flurbiprofen, ketoprofen, planopraphen, aspirin, sodium salicylate), glycyrrhizic acid. It is intended to provide an oral composition characterized by being blended with at least one component selected from anti-inflammatory agents such as dipotassium, β-glycyrrhizin, ε-aminocaproic acid and sodium azulene sulfonate.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The sap of the birch plant of the family Birchaceae used in the composition for oral cavity of the present invention can be collected from the plants of the family Birchaceae, such as birch, moss birch, yagawar birch, and yachi bim. , Betulaceae, Birch (Betulaceae) distributed in the southern Kuril Islands, Sakhalin, etc.
etula plyphylla var. jap
birch sap, which can be obtained from S. These sap can be collected by making a small hole in the trunk, and early spring is preferable at that time. About 99.3% of this overflowed sap is water, and the balance is solid content. Contains glucose, fructose as a sugar component, potassium, sodium, calcium, magnesium, manganese, iron, zinc, etc. as a mineral component,
It also contains amino acids, organic acids, and proteins.

[0008] If the collected birch sap is left as it is, spoilage, propagation of bacteria, etc. occur. Therefore, ethanol, paraoxybenzoic acid ester or a salt thereof, benzoic acid or a salt thereof, salicylic acid or a salt thereof, sorbic acid or a salt thereof, dehydroacetic acid or a salt thereof, isopropylmethylphenol, orthophenylphenol, cresol, is collected in white birch sap. It is desirable to appropriately add a preservative such as phenoxyethanol.

In the present invention, the amount of birch sap compounded is 0.001 to 10% by weight, preferably 0.01 to 5% by weight, based on the total amount of the oral composition. If the blending amount is less than 0.001% by weight, 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.

In the present invention, at least one drug selected from lysozyme, non-steroidal anti-inflammatory agents, dipotassium glycyrrhizinate, β-glycyrrhizinate, ε-aminocaproic acid and sodium azulenesulfonate can be blended. These medicinal agents can be blended in a usual effective amount range, and when they are used in combination with birch sap, they are more effective in preventing and treating periodontal diseases. Also, as a non-steroidal anti-inflammatory drug, indomethacin,
Examples include ibuprofen, flurbiprofen, ketoprofen, planoprafen, aspirin, sodium salicylate, and the like.

The oral composition of the present invention comprises a toothpaste, liquid toothpaste, mouthwash, ointment, cream, pasta,
It is provided as a preparation such as a troche, chewing gum, and a patch, and appropriate known ingredients are used depending on the preparation. 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; sweetening agents such as saccharin sodium; A preservative is appropriately mixed.

Antibacterial agents such as chlorhexidine, tetracycline, minocycline, iodine, acrinol, hinokitiol and penicillin; astringents such as salt, allantoin, aluminum chlorxyarantonate, aluminum dihydroxy allantoinate and tannic acid;
Hemostatic agents such as tranexamic acid, ε-aminocaproic acid, 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, phenol; procaine, etc. Local anesthetics; dentin strengthening agents such as various fluorine compounds and medicinal agents such as plaque formation inhibitors such as dextranase and mutanase can also be incorporated.

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

[0014]

EXAMPLES Next, the present invention will be described in detail with reference to examples. Needless to say, the present invention is not limited to these examples. Unless otherwise specified, [%] represents% by weight. 1. The test method and result of the capillary strengthening action and mucous membrane detaching action of birch sap are shown. (1) Capillary strengthening action (Test method) Wistar male rat (7 to 8 weeks old)
The hair was removed from the abdomen, and an ointment containing a base drug (Macrogol ointment, manufactured by Maruishi Pharmaceutical Co., Ltd.) mixed with a test drug efficacy 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 vascular strengthening effect was evaluated according to the criteria shown below. <Evaluation criteria> ++: Extremely effective ++: Effective ＋: Effective ±: Somewhat effective −: Ineffective

(2) Mucous membrane exfoliation action (Test method) As in the above (1), the mucous membrane exfoliation 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. 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.

(3) Comprehensive Evaluation For the final evaluation of the drug efficacy, the following criteria were evaluated in consideration of the results of the vascular strengthening action and the mucous membrane detaching action. <Evaluation Criteria> ⊚: Very good ∘: Good x: Poor The results are shown in Table 1.

[0017]

[Table 1]

As is clear from Table 1, the amount of birch sap incorporated into the composition of the present invention as an active ingredient is
It is preferably 0.001 to 10% by weight. When the amount is less than 0.001% by weight, 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.

2. Administration Method Furthermore, the following test was performed to compare the specificity of the birch sap vascularization effect due to the difference in administration method. Wistar male rats (7 to 8 weeks old) were used, and one group was similarly applied with a macrogol ointment containing 10% by weight of the birch sap, which had the best overall result in the test. 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, taking into consideration that the concentration of the medicinal agent was locally the same. The blood vessel strengthening effect of each animal was evaluated by the number of purpura as in the above test. Table 2 shows the results.

[0020]

[Table 2]

As is clear from Table 2, the blood vessel-enhancing effects of these drugs are shown to exert their effects only by local administration.

Next, Example 1 (pasta for oral cavity) was produced by a conventional method, and the effect of improving gingivitis was evaluated. The evaluation method will be described. <Subjects> Men with inflammatory changes in the gums 2
8 (23-33 years old) and 12 women (21-28)
(Years old) and divided into 4 groups of 10 people so that the inflammatory symptoms were almost the same. <Test Method> The above-mentioned 4 groups were designated as A to D groups, and oral pasta having the following formulation was given. Group A Oral pasta with birch sap 1% + sodium azulenesulfonate Group B Oral pasta with birch sap 1% + glycyrrhizin dipotassium Group C Oral pasta with birch sap 1% + ε-aminocaproic acid Group D Oral pasta base only, no drug blended The subject was given the same new toothbrush and after each meal the gingiva was massaged for 4 weeks. Brushing method was free.

<Determination of Gingivitis Improvement Effect> PMA In
It was evaluated by dex. 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.

[0024]

(Equation 1)

Example 1: Pasta ingredient for oral cavity Blending amount (%) Polyoxyethylene monostearate 2.0 Sorbitan monooleate 2.0 Cetyl alcohol 2.0 Palmityl alcohol 3.0 Propylene glycol 15.0 Carboxymethyl cellulose 5.0 Gelatin 1.0 Saccharin 0.2 Flavor 0.3 Birch sap Remainder 100.0

The results are shown in Table 3. As shown in the results, the oral composition of the present invention improves the weakened periodontal tissue by showing a blood vessel strengthening action, enhances resistance to physical stimulation of the tissue, and of periodontal disease such as gingivitis. Remarkably effective in prevention and treatment.

[0027]

[Table 3]

Example 2 Toothpaste Toothpaste was prepared with the following composition by a conventional method. Ingredient content (%) Dibasic calcium phosphate 45.0 Sodium carboxymethyl cellulose 1.0 Glycerin 20.0 Sodium lauryl sulfate 1.5 Perfume 1.0 Sodium saccharin 0.1 Birch birch sap Residual total 100.0

Example 3: Toothpaste A toothpaste was produced in the same manner as in Example 1 with the following composition. Ingredients Content (%) Calcium carbonate 45.0 Sodium carboxymethyl cellulose 1.0 Glycerin 20.0 Sodium lauryl sulfate 1.5 Perfume 1.0 Sodium saccharin 0.1 Birch birch sap Remainder 100.0

Example 4: Chewing gum A chewing gum having the following composition was produced by a conventional method. Ingredient content (%) Gum base 65.0 Mannitol 20.0 Sorbit 3.5 Fragrance 1.5 Birch sap 10.0 Total 100.0

Example: Mouthwash Mouthwashes having the following composition were produced by a conventional method. Ingredients Content (%) Ethanol 20.0 Saccharin sodium 0.15 Polyoxyethylene hydrogenated castor oil 2.0 Glycerin 5.0 N-lauroyl sarcosine sodium 0.5 Sucrose fatty acid ester 1.0 Perfume 1.0 Birch birch sap balance 100.0 in total

Example 6: Lozenge A troche was produced by a conventional method with the following composition. Ingredient content (%) Gum Arabic 6.0 Fructose 20.0 Glucose 20.0 Maltose 30.0 Fragrance 1.0 Birch birch sap Remainder 100.0

Example 7 Gingival Massage Cream A gingival massage cream was prepared by the conventional method with the following composition. Ingredients Content (%) White petrolatum 8.0 Stearyl alcohol 6.0 Propylene glycol 4.0 Polyethylene glycol 2000 25.0 Polyethylene glycol 4000 37.0 Cetyl alcohol 7.0 Birch sap Remainder 100.0

Example 8: Mouthwash Tablet A mouthwash tablet was produced by a conventional method with the following composition. Ingredients Content (%) Sodium hydrogen carbonate 55.0 Dibasic sodium phosphate 15.0 Polyethylene glycol 6000 3.0 Citric acid 12.0 Ethanol 6.0 Fragrances 4.0 Birch sap 5.0 Total 100.0

[0035]

The composition for oral cavity containing the birch sap of the present invention is excellent in preventing periodontal diseases such as gingivitis,
It has a therapeutic effect, and its effect is lysozyme, a non-steroidal anti-inflammatory drug (indomethacin, ibuprofen, flurbiprofen, ketoprofen, planoprafen, aspirin, sodium salicylate), dipotassium glycyrrhizinate, β-glycyrrhizinate, ε- It becomes effective by adding aminocaproic acid, sodium azulene sulfonate, etc.

Claims (5)

[Claims] 1. A composition for the oral cavity, which comprises a sap of a birch plant of the family Birchaceae. 2. The birch plant is a birch (Bet).
ula plyphylla var. japo
nica). The oral composition according to claim 1. 3. The sap of a birch plant of the family Birchaceae is 0.1.
It is 001-10 weight%, The composition for oral cavity of any one of Claim 1 or Claim 2 characterized by the above-mentioned. 4. Further, at least one selected from lysozyme, a non-steroidal anti-inflammatory agent, dipotassium glycyrrhizinate, β-glycyrrhizin, ε-aminocaproic acid and sodium azulenesulfonate is added. 1, any one of claims 2 and 3
The composition for oral cavity according to the item. 5. The composition for oral cavity according to claim 4, wherein the nonsteroidal anti-inflammatory agent is any one or more of indomethacin, ibuprofen, flurbiprofen, ketoprofen, planoprafen, aspirin, and sodium salicylate. .