JPS6258330B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a dentifrice composition, and more particularly, to a dentifrice composition containing an extract extracted from the herbal drug "Toki" using a specific solvent and having an excellent hemostatic effect. Periodontal diseases represented by gingivitis and alveolar pyorrhea are
Bleeding from the gums is particularly observed as a subjective symptom, and toothpaste compositions containing medicinal agents with hemostatic effects such as ε-aminocaproic acid and salt are used to prevent and treat this. However, there are various problems in terms of effectiveness, formulation stability, feeling of use, etc., and it is difficult to find one that is fully satisfactory. The present inventors, while continuing their intensive research to obtain a toothpaste composition with excellent hemostatic effect and without mucous membrane irritation or discomfort in the mouth, unexpectedly discovered an extract extracted from the herbal medicine "Toki" using a specific solvent. It has been found that by blending the extracted extract, a dentifrice composition with excellent hemostatic effect, stability, and usability can be obtained. In other words, Dangki has been used since ancient times as a blood supplement and analgesic and sedative, and is used in many Chinese herbal medicines for women's diseases.It is also used externally in Shiyun ointment, etc., to improve blood circulation, have anti-inflammatory effects, Although it has been shown to have an analgesic effect, no examples of its use as a hemostatic agent have been found. In addition, chronic bleeding from the gums, especially in periodontal diseases, is largely due to the activation of the fibrinolytic system in the in vivo hemostasis mechanism, and is difficult to treat with general anti-inflammatory agents and wound medicines. However, it has been found that a certain type of solvent-based extract has an excellent hemostatic effect on such gum bleeding. In addition, herbal medicine extracts are usually colored, and when added to toothpaste compositions, they may cause coloration, and because they contain various substances, the stability of the composition may be impaired due to the relationship with other ingredients in the composition. Furthermore, if the extract is used too much, the feeling of use will deteriorate, but even if the relevant extract is added, the degree of coloring of the dentifrice composition is low, stability is maintained, and the feeling of use is good, making it suitable for use as a dentifrice composition. It was found that the properties and feeling of use were fully satisfied. The present invention has been completed based on this knowledge, and we have found that the present invention is based on the above findings, and it has been found that an extract extracted with one or more solvents selected from the group consisting of ether, ester, ketone, and alcohol is blended. The present invention provides a dentifrice composition comprising: The dentifrice composition of the present invention has an excellent hemostatic effect, and at the same time, the dentifrice extract contained in the dentifrice composition exhibits an excellent hemostatic effect without impairing the properties and feel of the dentifrice, and without problems such as irritation of the oral mucosa. It also has various effects, and is extremely useful in the prevention and treatment of periodontal diseases. Specific examples of solvents to be used include ethers having 2 to 8 carbon atoms such as ethyl ether, isopropyl ether, and ethylene glycol diethyl ether, ethyl acetate, methyl propionate, isobutyl formate, methyl lactate, and butyl acetate. Lower alkyl esters having 1 to 4 carbon atoms of organic acids having 1 to 4 carbon atoms, acetone, methyl ethyl ketone,
Ketones having 3 to 9 carbon atoms such as methyl isobutyl ketone and methyl propyl ketone, methyl alcohol, ethyl alcohol, propyl alcohol,
Examples include alcohols with 1 to 5 carbon atoms such as butyl alcohol and amyl alcohol, and solvents that have a hydroxy group, ketone group, or ether bond in one molecule such as acetonylmethanol, cellosolves, and carbitols. Included. Furthermore, when water is used as a solvent, the stability of the toothpaste decreases, but in the case of a water-soluble solvent, there is no problem in mixing water up to about 30% in the extraction solvent, and such water-containing solvents can also be used as the solvent of the present invention. included in. These solvents may be used alone or in combination of two or more, and in particular, ethyl ether, ethyl acetate,
Low boiling point substances such as acetone, methyl alcohol, and ethyl alcohol are preferred for extraction operations. Extraction of the return can be done according to the conventional method,
For example, a solvent is added to dried shredded material. The amount of solvent used is not particularly limited, and any amount may be used as long as the active ingredient is sufficiently extracted, but usually, the amount of solvent used is 3 to 20 times the weight of the material to be extracted, and the extraction operation is performed for 3 times. You can repeat it several times. Also,
Extraction efficiency is better if the temperature is moderately heated during extraction, but
Excessive heating increases the degree of coloration of the extract, so it is preferable to extract for a long time without refluxing. Normally, one extraction time is about 3 to 48 hours at room temperature to 60°C. The obtained extract is used in the form of a concentrated extract after removing the solvent according to a conventional method. In addition, the extract obtained by extracting Dongki with water or 50% aqueous ethyl alcohol, or its concentrate, may be re-extracted in the same manner with the above solvent, and the resulting extract can be extracted directly from Dongki. There is no difference in terms of effectiveness. The amount of the obtained extract can be selected as appropriate;
Its hemostatic effect, its influence on the stability of toothpaste properties,
From the viewpoint of feeling in use, it is usually preferably 0.005 to 5% (weight %, same hereinafter) based on the total amount of the dentifrice composition. Next, the results of testing the hemostatic effect of extracts using various solvents and the effects on the properties of toothpaste will be shown. The hemostatic effect of tooth brushing can be confirmed by the inhibitory effect on the activity of fibrinolytic enzymes in the in vivo hemostatic mechanism, ie, plasmin, which is an enzyme that degrades fibrin and causes bleeding, and was tested as follows. (1) Preparation of extract of Oriental chinensis Approximately three times the amount of solvent was added to 100 g of dried shredded Oriental chinensis and extracted at 60° C. or lower for 3 hours. This extraction operation was repeated three times, the extracts were combined, and the solvent was removed under reduced pressure to prepare an extract. (2) Preparation of sample solutions The obtained extracts were dispersed and dissolved in 0.15M salt-added 0.01M phosphate buffer (PH7.8) to prepare sample solutions of various concentrations. (3) Preparation of fibrin plate Wallen et al., Haemostasis,
4, 110, 1975), agarose 100
mg of 0.15M NaCl in 0.01M phosphate buffer (PH7.8)
After heating and dissolving the mixture in 10 ml, the mixture was cooled to 40°C, and 16.6 mg of pusminogen-removed fibrinogen (manufactured by Daiichi Chemical Co., Ltd.) was dissolved therein. Add 0.1 of thrombin solution (100 units/ml, Mochida Pharmaceutical Co., Ltd.) to the obtained solution.
After dropping ml, pour it into a chalet (diameter 9cm),
Cool and solidify at room temperature, then place a diameter 6 in the center.
Fibrin plates were prepared by drilling mm holes. (4) Measurement of plasmin activity inhibition Ambrus et al.
Pediatrics, 32, 10, 1963), add 0.1 ml of plasmin solution (0.4 units/ml, manufactured by Sigma) to 0.1 ml of the sample solutions of various concentrations prepared above.
and after 30 minutes, into the holes of the fibrin plate,
20μ of each was injected. After standing at 37°C for 20 hours, the fibrin dissolution area was measured and compared with the fibrin dissolution area of the plate without the sample solution (added 0.1ml of plasmin solution), and the sample solution concentration required for 50% suppression of plasmin activity ( ID ₅₀ mg/ml) was determined. In addition, the effect on the properties of toothpaste was evaluated after toothpaste containing 1% of each extract based on the total amount was obtained according to the formulations in Examples 1 and 2 below, and was kept at 55°C for 1 month and 3 months. Properties were evaluated according to the following criteria. ○: No discoloration or softening was observed, and there were no particular problems in terms of properties. Δ: Slight discoloration or softening is observed, but there is no discomfort during use and it is acceptable as a product. ×: Significant discoloration and softening, giving a strange feeling in use and not acceptable as a product. The results are shown in Table 1 below. As a control, the results of a similar test using tranexamic acid, which is known as a hemostatic agent, as well as similar extracts of Osteoplasty, which is a herbal drug that has been found to have a hemostatic effect, and Cypress leaf are also shown.

[Table] As is clear from these results, our ethyl ether, ethyl acetate, acetone, ethyl alcohol, and methyl alcohol extracts exhibit a much higher plasmin activity inhibitory effect than extracts such as water and hexane, and have a hemostatic effect. It exhibits excellent hemostatic effect, which is higher than that of the herbal medicine known as Osteoplasty and Cypress leaf extract. Furthermore, the properties of toothpastes containing these extracts do not exhibit any discoloration or softening, which is seen with water extracts, and do not affect the stability of the properties of toothpastes. Furthermore, even a 70% ethyl alcohol aqueous solution extract exhibits a sufficient plasmin activity inhibitory effect, and the toothpaste containing it hardly discolors or softens, maintaining properties that are sufficiently satisfactory as a toothpaste. Although it is preferable not to use water as a solvent, it is acceptable to mix water as long as it is about 30%. Furthermore, the water or alcohol extract of Toki was re-extracted as follows, and the hemostatic effect of the re-extract and the influence on the properties of toothpaste were tested in the same manner as in Table 1. Re-extraction of Toki (1) 100 g of dried shredded Toki was refluxed with 0.3 of water and extracted for 3 hours. This extraction operation was repeated three times, and the extracts were combined and concentrated under reduced pressure at below 60°C.
Approximately three times the amount of re-extraction solvent was added to each of the obtained concentrates, and re-extraction was performed at room temperature for 1 hour. This operation was repeated three times, the resulting extracts were combined, and the solvent was removed under reduced pressure to prepare an extract. (2) Re-extraction was performed in the same manner using ethyl alcohol instead of water. Table 2 shows the results of the hemostatic effect and the influence on the properties of toothpaste.

[Table] As shown in Table 2, even if extracted once with water and re-extracted, an extract with excellent hemostatic effect can be obtained, and the properties of toothpaste will not be impaired. Thus, the dentifrice composition of the present invention can be made into a dosage form such as a toothpaste, powdered dentifrice, or liquid dentifrice according to a conventional method. Other ingredients may be any commonly used ones, such as abrasives such as dicalcium phosphate, calcium carbonate, and aluminum hydroxide, binders such as sodium carboxymethyl cellulose and carrageenan, sodium lauryl sulfate, and sodium lauroyl sarcosine. surfactants, wetting agents such as glycerin and sorbitol. Furthermore, other medicinal agents may be used in combination, such as various fluorine compounds, aluminum allantoinate, glycyrrhizinate, chlorhexidine, hinokitiol, dextranase, lysozyme, and common salt. Next, the present invention will be explained in more detail with reference to Examples. Example 1 4 ethyl ether was added to 1 kg of shredded mushrooms, extracted at 35°C for 3 hours, and the extract was filtered. This operation was repeated three times, the liquids were combined, and the solvent was removed under reduced pressure to obtain about 20 g of extract. Using this extract, a toothpaste was manufactured according to the following recipe using a conventional method. Ingredients % Dibasic calcium phosphate dihydrate 45.0 Sodium carboxymethyl cellulose 0.5 Carrageenan 0.5 Glycerin 10.0 Sorbitol 10.0 Sodium lauryl sulfate 1.5 Flavoring 1.0 Sodium satucharin 0.2 Toki extract 0.5 Water Adjusted to 100% The hemostatic effect of the obtained toothpaste was evaluated as follows. I tested it thoroughly. (1) Selection of subjects 20-51 subjects with constant bleeding reactions even at rest
We selected 16 male and 4 female subjects aged 10 to 20 years old, and divided them into 2 groups, 10 each from the experimental group and 2 from the control group, so that people with the same level of bleeding from their gums were evenly included.
The subjects in the experimental group (A to J) received the toothpaste of Example 1, and the subjects in the control group (K to J) received the toothpaste of Example 1.
For T), a toothpaste prepared by removing the Toki extract from the formulation of Example 1 was used. (2) Measurement of hemostasis effect Each subject was not given any special brushing instructions, but was instructed to brush after every meal using the same toothbrush, and was allowed to continue brushing their teeth with the above toothpaste for 4 weeks. During this period, each subject's saliva was collected every week from the start of the test.
HemacombiStick (urine test strips manufactured by Miles Sankyo Co., Ltd.) was applied to this for 30 seconds, and after being left for another 30 seconds, the amount of occult blood in the saliva was measured by comparing it with the colorimetric chart on the test strip container label. Please note that saliva should be collected around 10 a.m. or 3 p.m., avoiding immediately after brushing teeth, and the measurement results should be negative (-) to 3:00 p.m. for the amount of occult blood.
Divided into stages up to large amount (〓), -: 0, ±:
0.5, +:1, +~〓:1.5,〓:2,〓~〓:
2.5, =: Expressed with a score of 3. The results are shown in Table 3.

[Table] As is clear from the results, the dentifrice composition of the present invention exhibits an excellent hemostatic effect. Also, during the exam,
Subjects were asked to evaluate the toothpaste properties and feel of the toothpaste, and no problems were found. Example 2 4 ethyl alcohol was added to 1 kg of the shredded mushrooms, extracted at 60°C for 3 hours, and the extract was filtered. Add 2 more ethanol to the residue and further heat at 60°C.
The mixture was extracted for 3 hours and the extract was filtered. Repeat this latter extraction operation once more, combine all the liquids, and
The solvent was distilled off under reduced pressure at temperatures below 0.degree. C. to obtain about 100 g of extract. Using this extract, a toothpaste was manufactured according to the following recipe using a conventional method. Ingredients % Aluminum hydroxide 45.0 Sodium carboxymethyl cellulose 0.5 Carrageenan 0.5 Glycerin 10.0 Sorbitol 10.0 Sucrose fatty acid ester 2.0 Sodium lauroyl sarcosine 0.5 Sodium saccharin 0.2 Flavor 1.0 Toki extract 0.1 Water Adjusted to 100% Example 3 Finely chopped Toki 1Kg A 70% ethyl alcohol aqueous solution 4 was added to the solution, and after standing at room temperature for 2 days, the extract was filtered. Add 2 more ethanol to the residue,
After standing for another day, the extract was filtered. Repeat this latter extraction operation once more, combine all the liquids,
The solvent was distilled off under reduced pressure at 65° C. or lower to obtain about 200 g of extract. Using this extract, a toothpaste was manufactured according to the following recipe using a conventional method. Ingredients % Calcium carbonate 40.0 Sodium carboxymethylcellulose 0.5 Carrageenan 0.5 Glycerin 13.0 Sorbitol 7.0 Sodium lauryl sulfate 2.0 Sodium saccharin 0.1 Flavor 1.0 Toki extract 1.0 Water Adjustment to 100% Example 4 Add 50% methyl alcohol aqueous solution to 1 kg of shredded Toki was added, refluxed and extracted for 3 hours, and the extract was filtered. Repeat this operation 3 times, combine all the liquids, and
The mixture was concentrated under reduced pressure to 2.degree. C. or below. After adding ethyl ether 2 to this extract and mixing well, the ethyl ether layer was separated. This operation was repeated three times, the ethyl ether extracts were combined, and the solvent was removed under reduced pressure to obtain about 25 g of extract. Using this extract, a toothpaste was manufactured according to the following recipe using a conventional method. Ingredients % Dibasic calcium phosphate dihydrate 50.0 Sodium carboxymethyl cellulose 0.6 Carrageenan 0.4 Glycerin 8.0 Sorbitol 12.0 Sodium laurate 2.5 Sodium saccharin 0.1 Flavoring 1.0 Toki extract 0.01 Water Adjusted to 100%

Claims (1)

[Scope of Claims] 1. A toothpaste composition characterized by containing an extract extracted with one or more solvents selected from the group consisting of ethers, esters, ketones, and alcohols. 2 The extract is added in an amount of 0.005 to 5% relative to the total amount of the composition.
% by weight of the dentifrice composition of item 1 above.