JPS643163B2 - - Google Patents

Description

[Detailed description of the invention]

INDUSTRIAL APPLICATION FIELD The present invention provides oral compositions, more specifically, as medicinal agents for the prevention and remission of chronic marginal periodontitis.
The present invention relates to oral compositions such as toothpastes and topical gingival preparations that stably contain aprotinin. Prior Art Chronic marginal periodontitis, so-called alveolar pyorrhea, is one of the major diseases in dentistry, and its prevention,
Treatment has become a very important issue in terms of oral hygiene. In recent years, it has been revealed that the fibrinolytic system (fibrinolytic system) is activated in the gingiva, which exhibits inflammatory symptoms such as bleeding, swelling, redness, and drainage, which are symptoms of alveolar pyorrhea. surgery elly, 35
vol., p. 818, 1973), attempts have been made to incorporate substances that inhibit plasmin, an enzyme involved in the fibrinolytic system, into oral compositions as medicinal agents for the prevention and remission of alveolar pyorrhea. Representative examples of such medicinal agents include epsilon aminocaproic acid and tranexamic acid. However, epsilon aminocaproic acid and tranexamic acid are stable when added to oral compositions, but have a drawback in that they have a low plasmin suppressing effect. On the other hand, as a substance with a high plasmin suppressing effect,
Aprotinin, a polypeptide isolated and purified from animal organs, is known. However, when aprotinin is added to an oral composition, it is usually considered an essential ingredient for the purpose of thickening or caking to maintain the dosage form of the oral composition. Due to the influence of the thickening agent in the composition, it has the disadvantage of becoming very unstable and prone to expiration, and so far, no oral composition has been found that stably contains aprotinin. Purpose of the Invention In view of the above circumstances, the present inventors conducted intensive research in order to obtain an oral composition in which aprotinin is stably blended, and as a result, surprisingly, they discovered that various oral compositions that are usually blended in oral compositions Among the thickening agents, it was discovered that only sodium carboxymethyl cellulose does not specifically affect aprotinin and keeps aprotinin stable, leading to the completion of the present invention. Structure of the Invention That is, the oral composition of the present invention is characterized by containing aprotinin as a medicinal agent and sodium carboxymethyl cellulose as a thickening agent. According to the present invention, aprotinin can be stably retained in the oral composition for a long period of time,
Its high plasmin suppressing effect can be used to prevent and relieve alveolar pyorrhea. As mentioned above, aprotinin is a polypeptide isolated and purified from animal organs, usually bovine pancreas, and has a basic structure of a polypeptide with a molecular weight of approximately 6,500, consisting of 16 types of 58 amino acids linked together in a chain. In the present invention, any commonly available aprotinin can be used, such as commercially available trasylol (manufactured by Bayer) and anticrein (manufactured by Teikoku Kinki Co., Ltd.). The blending amount is 0.0001 to 1.0% (weight%,
(the same applies hereinafter), preferably 0.001 to 0.1%. The carboxymethyl cellulose sodium may be any of those commonly used as a thickening agent, and from the viewpoint of solubility in water, those having a degree of substitution of OCH ₂ COONa of 0.4 or more, preferably 0.7 or more are suitable. Generally, from the viewpoint of dosage form stability, it is 0.5 to 3.0%, preferably 1.0% to the entire oral composition.
It is blended at a rate of ~2.0%. The oral composition of the present invention can be made into a dosage form such as a toothpaste, an oral paste, a gingival paste, etc. in accordance with a conventional method, and other ingredients are not particularly limited, and any commonly used ones can be used. But that's fine. For example, in the case of toothpaste, wetting agents such as glycerin and sorbitol, abrasives such as dicalcium phosphate, calcium carbonate, aluminum hydroxide, anhydrous silicic acid, calcium pyrophosphate, and insoluble sodium metaphosphate, sodium lauryl sulfate, and N-acylsarcosine. Foaming agents such as sodium, sucrose fatty acid ester, alkyl diethanolamide,
Sweeteners, flavors, etc. may be included, and other medicinal agents such as sodium monofluorophosphate, chlorhexidine, and other anti-inflammatory agents may also be included. Effects of the Invention Next, the results of testing the stabilizing effect of sodium carboxymethylcellulose on aprotinin will be shown. Test 1 Dissolve 3 mg of aprotinin in 1 ml of water and add this solution.
Add 0.8ml of aqueous solutions of various thickeners to 0.2ml and heat at 37°C.
It was stored for 40 days. Dilute this stored solution 10 times with water and add 0.1M Tris-HCl buffer to 0.2ml.
ml, 1.0 ml of 0.1% N-benzoylarginine paranitroanilide solution was added. To this, 0.1 ml of 0.02% trypsin solution was added and reacted at 37°C for 30 minutes, and then 1 ml of 20% acetic acid was added to stop the reaction. The amount of liberated paranitroanilide was measured by absorbance at a wavelength of 410 nm, and the activity of aprotinin was calculated from this value. Similarly, the activity of aprotinin before storage was calculated, and the residual activity rate (%) of aprotinin after storage was examined. As a control, a system without the addition of a thickening agent was also tested in the same manner. The results are shown in Table 1.

[Table] As shown in Table 1, among various thickening agents, aprotinin is specifically kept stable only when carboxymethyl cellulose sodium is used. Test 2 Aprotinin-containing toothpaste and gingival liniment having the following formulations were prepared according to a conventional method. Toothpaste formulation Ingredients % Calcium phosphate dibasic 45.0 Sodium lauryl sulfate 1.5 Sorbitol 20.0 Sodium carboxymethylcellulose 1.0 Sodium satucalin 0.15 Fragrance 1.0 Aprotinin 0.001 Water Gingival liniment formulation adjusted to 100% Ingredients % Sodium carboxymethylcellulose 1.0 Glycerin 40.0 Aprotinin 0.01 Water 100 After storing the obtained toothpaste and gum paste at 37℃ for 40 days, the aprotinin activity of the sample was calculated in the same manner as in Test-1 above, and the residual activity of aprotinin was compared with the activity immediately after adjustment. I checked the rate. As a result, the residual activity rate was 91% for the toothpaste and 95% for the gingival paste, indicating that aprotinin remained stable in both formulations. Examples Next, the present invention will be explained in more detail by giving examples. Example 1 A toothpaste having the following formulation was manufactured according to a conventional method. Ingredients % Dibasic calcium phosphate 45.0 Sorbitol 25.0 Sodium carboxymethylcellulose 1.0 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Flavor 1.0 Aprotinin 0.001 Water Adjusted to 100% Example 2 A gingival liniment with the following formulation was produced according to a conventional method. Ingredients % Sodium carboxymethylcellulose 1.0 Glycerin 20.0 Aprotinin 0.01 Water Adjusted to 100%

Claims (1)

[Claims] 1. An oral composition comprising aprotinin as a medicinal agent and sodium carboxymethyl cellulose as a thickening agent.