JPS6185304A - Auxiliary for dental treatment - Google Patents

Abstract

PURPOSE:An auxiliary agent for treating periodontal diseases that contains fibrinogen as a major ingredient, further a ceramic material, fibronectin, blood coagulation factor XIII and antibiotic, thus showing increased biocompatibility of the ceramic material. CONSTITUTION:The objective auxiliary agent for treating periodontal diseases contains, as a major ingredient, fibrinogen which is obtained from human or animal plasma. Fibrinogen is solidified and converted into fibrin by combining it with thrombin or calcium chloride as a coagulation agent to give a composition for treating periodontal diseases in which the ceramic materialis dispersed in gelatlinous fibrin. When needed, the affected position to be treated for periodontal diseases is previously filled with the ceramic material and a combination of thrombin or calcium chloride solution with fibrinogen solution or powder is casted therein or vice versa.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to an invention for a new use of fibrinogen.

[Conventional technology]

In the dental field, infection and inflammation of the periodontal tissue causes granulomatization of the periodontal tissue, causing loosening and movement of the teeth. The current treatment for this caries disease is to maintain the current state of the alveolar bone, and the only treatments for advanced cases are tooth extraction or fixation with a bridge bridge.

[Problem that the invention seeks to solve]

To treat this disease, the present inventor first attempted alveolar bone reconstruction using ceramic materials. Among these ceramic materials, hydroxyapacite (hereinafter abbreviated as 11AP), tricalcium phosphate (hereinafter abbreviated as TCP), alumina, carbon, etc., which have excellent biocompatibility, are being developed as artificial bones. are collecting. H.A.
A block-shaped P is used as a bone substitute, but the present inventor used it in the form of a fine powder for alveolar bone reconstruction. However, ceramic strips have no adhesiveness to each other, are difficult to manipulate during insertion, may scatter into surrounding tissue, and are difficult to maintain their shape even after being densely packed. . In particular, it is extremely difficult to form delicate alveolar bone morphology.

[Purpose of the invention]

An object of the present invention is to provide an adjuvant for periodontal disease treatment. More specifically, the object of the present invention is to provide an adjuvant for periodontal disease treatment in order to improve the compatibility of ceramic materials with living organisms. Another object of the present invention is to provide a new medical use for fibrinogen, which has conventionally been used as a tissue adhesive. The object of the present invention is to provide an adjuvant for periodontal disease treatment that improves the biocompatibility of ceramic materials.

[Structure of the invention]

The present invention consists of a periodontal disease treatment adjuvant containing fibrinogen as a main component, which is characterized by increasing the tissue compatibility of ceramic materials during periodontal disease treatment using ceramic materials.

[Description of the Invention] The fibrinogen used in the present invention is obtained from human or animal blood extraction. From the viewpoint of biocompatibility, when the target is a human, it is preferable to use fibrinogen obtained from human supplementation, and when the target is an animal, it is preferable to use fibrinogen obtained from the animal's plasma as the raw material.

As such fibrinogen, it is possible to use dried medical fibrinogen manufactured in accordance with the Biological Products Standards (1979, pp. 201-203) supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare.

In addition, coagulant proteins such as fibrotin and blood coagulation agents are added as additives, and monomers such as sodium citrate and glucose, fluwatose, mannilla) are added as stabilizers, as well as other drugs (e.g. penicillin). , Streptomycin Specifically, "Fibrinogen Midori" (trade name, ((
This is a dry preparation containing, in addition to pharmaceutical dry fibrinogen, fibronectin, coagulant proteins such as factor 1, citric acid, and glucose.

In this way, fibrinogen and various additives may be mixed together, or they may be dissolved separately and then mixed together at the time of use.

When using fibrinogen, add distilled water for injection or pI
Dissolve in IG~7 low salt buffer solution i. As this low salt concentration buffer, a 0.01 to 0.03 molar citric acid buffer is suitable. The dissolution temperature is 32 to 36°C, and it is preferable to maintain the inside of the bottle containing fibrinogen under reduced pressure during dissolution. Under such dissolution conditions, dry fibrinogen powder dissolves within a range of about 2 to IOW/V%. Further, fibrinogen may be used in powder form. As detailed below, fibrinogen is solidified into fibrin by adding thrombin as a solidifying agent and calcium chloride when used in periodontal disease treatment as an adjuvant for periodontal disease treatment. Normal thrombin 1
It is preferable to include ~500 N I H units/mj and calcium chloride 10-100 rnmal/mA'; below the lower limit, fibrinogen solidification may be insufficient; on the other hand, if the upper limit is In many cases, even if added in excess of this amount, the assimilation effect will not change much.

In order to prevent fibrin from being dissolved depending on periodontal disease treatment, a protease inhibitor may be added to the mixed solution. Plasmint harmful agents can be preferably used as protease inhibitors, such as aprotinin, epsilon aminocaproic acid, planexamic acid, soybean l-lipsin inhibitors, and the like. The amount of protease inhibitor added is 7ik:1. O O~5000KIE units/
It is about ++t'.

When treating periodontal diseases using the fibrinogen of the present invention, powder or granules of ceramic materials,
Alternatively, granules or blocks made from powder are used. The fibrinogen and the ceramic material may be mixed by Kawasaki, or may be prepared in advance as a composition.

Any ceramic material may be used as long as it is biocompatible, such as HAP and TCP.

Tetracalcium phosphate, oxyavatai I-, calcium birophosphate, fluorine abatai 1. , a compound in which part of the water 6 monoacid group of HAP is substituted with fluorine, alumina, and carbon are exemplified. As a preferable example, ■(AP, T
CP is exemplified. Otonori J paddy grain size 100-800
It is preferable that the material is in the form of granules or fine powder of .mu., but a block-like material may be used if desired.It is particularly preferable that the material is fired at a high temperature of 500.degree. C. or higher. The ceramic material that can be used in the present invention may be one that is artificially synthesized by a known manufacturing method such as a wet method, a dry method, or a heat treatment method, or one that is derived from a natural product.

When a mixture of fibrinogen and ceramic material and a solution containing thrombin and calcium chloride are mixed and stirred, thrombin and calcium chloride insolubilize fibrinogen into fibrin in about 2 to 3 minutes, and the ceramic material is dispersed in the colloidal fibrin. A composition for treating periodontal diseases is obtained. Since it takes about 2 to 3 minutes for fibrinogen, thrombin, and calcium chloride to solidify, the mixed solution of thrombin and calcium chloride is added to the fibrinogen solution or powder, then the ceramic material is added thereto, and the mixture is stirred. A composition for treating periodontal disease can also be obtained.

In some cases, the area to be treated for periodontal disease may be filled with ceramic sui-i material in advance, and then 1 of the mixed solution mixed with fibrinogen solution or powder is poured into the area.
Alternatively, it is also possible to pour the mixed solution with the fibrinogen solution or powder added thereto first, and fill it with the ceramic material later.

〔effect〕

When used in the treatment of periodontal disease, ceramic materials can stabilize teeth and avoid tooth extraction in advanced cases.

Fibrin is a hard protein obtained by the action of fibrinogen and thrombin, and has the function of adhering the wound surface. A: Fibroblasts develop and eventually turn into fibrocytes, which fix the tissue and generate blood vessels within the tissue. Therefore, in the present invention, the adhesive action of fibrin holds the ceramic material in a fixed state, promoting the fixation of the ceramic to the alveolar bone, and
It can promote new blood vessel formation, form new bone, and speed up the repair of living tissue.

Furthermore, since the present invention contains fibronectin, it strengthens fibroblast production and increases FfiCtOpXll.
It can be expected to strengthen the crosslinking of fibrin.

In this way, the fibrinogen of the present invention can improve the tissue compatibility of ceramic materials and give them shape, making it possible to treat periodontal diseases more efficiently, and to improve the periodontal Provide adjuncts for disease treatment.

Example 1 60 μg of fibrinogen extracted and purified from human blood, 100 units of No. W convict, 20 mg of fibronectin, and 54.0 mg of hydroxyapatite powder (calcined at 900°C)
7 ml of thrombin 4 NIH units in a 9% solution of citrate buffer (pH 6)! .

40m containing aprotinin 3000 KIE units/me
A composition to which 1 mp of M calcium chloride solution was added was prepared, mixed, and solidified to prepare a composition for treating periodontal disease. Next, the above-mentioned composite acid was filled onto the resorbed alveolar bone, and the progress was observed after 4 weeks. :) As a control, B lapse was also observed in the sample not filled with anything.

As a result, when the periodontal disease treatment composition prepared using fibrinogen of the present invention was filled, HAP remained unabsorbed into the tissue, and the fibrous tissue invaded the HAP to firmly fix the tooth.

Example 2 + (TCP was used instead of AP (calcined at 11, 50°C), but the same procedure as in Example 1 was followed, and the same effect was obtained.

Claims (4)

[Claims] (1) A dental treatment auxiliary agent characterized by using fibrinogen as an auxiliary agent for periodontal disease treatment. (2) The dental treatment aid according to claim (1), further comprising a ceramic material. (3) Fibronectin and/or blood coagulation factor XIII
Claim No. 1 characterized in that it further contains (
The dental treatment aid described in item 1) or item (2). (4) The dental treatment aid according to claim 1, 2, or 3, further comprising an antibiotic.