JPS62223114A - Slowly-releasing remedy for periodontosis - Google Patents

Abstract

PURPOSE:To produce the titled remedy capable of releasing the active component over a long period without causing pain to the diseased part by the application to periodontal pocket or periodontal site, by mixing a substance effective in remedying periodontosis to a mixture of a water-insoluble polymer and a water-soluble polymer and forming the obtained mixture. CONSTITUTION:A water-insoluble polymer (e.g. ethylcellulose, cellulose acetate, copolymer of methacrylic acid and chlorotrimethyl-ammonium methacrylate, etc.) is mixed with a water-soluble polymer (e.g. methylcellulose, sodium alginate, PVA, etc.) at a weight ratio of 1/9-7/3 (former polymer to latter polymer in dry basis). The mixture is mixed with a substance effective as a remedy for periodontosis and formed in the form of sheet, film or rod. The remedy is inserted in or applied to the periodontal pocket or periodontal site of a patient of periodontosis.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a periodontal disease treatment agent for direct application to a diseased site, and more specifically to a periodontal disease treatment agent for insertion or pasting into periodontal pockets or periodontal sites of patients with periodontal disease. This article relates to a sustained-release periodontal disease treatment agent that, when applied, can release ingredients over a long period of time without causing pain to the patient.

Prior Art Periodontal disease is a general term for inflammatory diseases in the periodontal tissue, and includes various pathological conditions that appear depending on the degree of progression of the disease and the age of the patient, and there is still no clear classification. Not done.

Generally, it takes the form of an inflammatory disease that spreads from the gingival margin to the deep alveolar bone, and as the disease progresses, inflammation is limited to the gingival area (gingivitis), and the inflammation reaches the alveolar bone, resulting in chronic periodontal disease. It is broadly classified into flame.

There are also special periodontal diseases such as juvenile periodontitis and acute ulcerative periodontitis.

Among these, periodontitis, which was once called alveolar pyorrhea, is caused by inflammation of the gums, the formation and growth of periodontal pockets, and
It is a disease whose main symptoms are bleeding and drainage from periodontal pockets, followed by alveolar bone resorption, which eventually leads to tooth movement and falling out.

child,! 1) Regarding the etiology of periodontal disease, currently, local,
In particular, researchers agree that it is a type of bacterial infection caused by bacteria living in plaque in periodontal pockets.

Traditionally, periodontal disease treatment includes scaling and root planing to thoroughly remove plaque, especially plaque and tartar in subgingival periodontal pockets, and gingivectomy to eliminate periodontal pockets. Alternatively, surgical scraping for the purpose of removing inflamed tissue has been performed with some success.

For drug therapy, drugs such as bactericidal agents, anti-inflammatory agents, plaque dissolving agents, and hemostatic agents are used, and they can be taken orally or with toothpaste,
It is used as a pine surge agent such as ointment.

However, none of these can be said to be effective therapeutic agents for periodontal disease. That is, in the case of oral preparations, it is difficult to selectively transfer the drug to the periodontal region, which is the lesion, and it is difficult to control subgingival plaque with toothpastes and pine surgers.

In recent years, with the aim of controlling subgingival plaque and treating inflammation, which has been considered difficult with conventional drug therapy, strips made of drugs and polymers are administered directly to the lesion to selectively reach the lesion site. By doing so, it has become possible to perform more effective treatment compared to conventional drug therapy.

For example, hollow fiber
r) containing a bactericide and implanting it in the periodontal site [J. M. Goodson et al., Journal of Clinical Periodontology (J.
, C11nical.

Periodontology) l 979: 6
: 83-92), a method of inserting strips consisting of an insoluble polymer such as polyethyl methacrylate and a bactericide into the periodontal pocket [Aradi (M, A dd
y) et al., Journal of Cerebral Diseases (J, p.
eriodontal), November issue 693 (1982)
) A method of inserting Naro Strips made of water-soluble polymers and drugs into periodontal pockets, etc. (Publication Publication No. 59-222406) has been reported.

In drug therapy for periodontal disease, preparations in which a therapeutically active ingredient is formed into a film or sorted form together with a polymer and directly administered to periodontal pockets or periodontal sites are extremely useful.

However, when only water-soluble polymers are used in formulation, the local affinity at the site of administration is compromised, so while the burden on the patient is small, the drug remains at the site of application for a long time. The disadvantage is that the Xuo effect cannot be obtained. On the other hand, when only insoluble polymers are used in formulation, the residence time of the drug becomes long and the sustained release effect of the drug is excellent, but it lacks local affinity, giving the patient a foreign body sensation and causing pain. The disadvantage is that it tends to cause

Therefore, there is a need for a therapeutic agent for periodontal disease that has high affinity at the application site, has a long local retention time, and has an excellent sustained release effect when directly applied to the lesion site.

Purpose and Structure of the Invention In view of the above circumstances, the present inventors have developed a method for periodontal disease that does not cause discomfort such as pain to patients when applied to periodontal pockets or periodontal sites, and that has a sustained release effect. As a result of intensive research aimed at developing a therapeutic agent, we discovered that by mixing water-insoluble polymers and water-soluble polymers in an appropriate ratio and dispersing substances effective in periodontal disease treatment, The inventors have found that the above object can be achieved and have completed the present invention.

That is, the present invention provides periodontal pockets or teeth in the form of a sheet, film, or rod, in which one or more substances effective for the treatment of periodontal disease are dispersed in a mixture of a water-insoluble polymer and a water-soluble polymer. To be inserted or pasted around the circumferential area,
The present invention relates to a sustained-release periodontal disease therapeutic agent.

In the formulation of the present invention, the blending ratio of water-insoluble polymer to water-soluble polymer is preferably in the range of 1:9 to 7:3 in terms of dry weight ratio.

Examples of water-insoluble polymers suitable for use in the formulations of the invention include ethylcellulose, cellulose acetate, methacrylic acid/trimethylammonium methacrylate copolymer, dimethylaminoethyl methacrylate/methacrylic acid copolymer, polyvinyl acecoolate. - methylaminoacetate and cellulose acetate/dibutylhydroxopropyl ether.

Examples of water-soluble polymers used in the formulation of the present invention include methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylenecellulose, hydroquine ethylcellulose, sodium alginate, propylene glycol alginate, pullulan, tragacanth, xanthan gum, Mention may be made of chitosan, polyethylene oxide, polyvinyl vicritone, polyhinyl alcohol, polyacrylic acid and polymethacrylic acid, and salts thereof.

In addition, the active ingredients used in the preparation of the present invention may be any effective ingredients for the treatment or prevention of periodontal disease, such as acrinol, chlorhexidine, protein silver, iodoglycerin, phenol, benzene chloride, etc. Drugs with bactericidal action such as ruconium and cetylpyridium chloride; drugs with antibacterial action such as ampicillin, tetracycline, hensylpenicillin, clindamycin, cephalexin, erythromycin, chloramphenicol, and fradiomycin monoacid; Substances with anti-inflammatory effects such as ibuprofen, indomethacin, ketoprofen, mefenamic acid, antipyrine, pranoprofen, ibufenac, thiaramide hydrochloride, prednisolone, dexamethacin, triamunolone acetonide, prostaglandin, dextranase, protease, amylase, etc. Substances that have a plaque dissolving action, substances that have a collagenase inhibitory action obtained from crude drug extracts such as Gomish and Asenyaku, tetracaine hydrochloride,
Mention may be made of substances having a local anesthetic effect such as amino acids, ethyl fragrant, antihistamines such as chlorpheniramine maleate, nophenhydramine, and hemostatic agents such as tranexamic acid.

To prepare the formulations of the invention, one or more of the above active ingredients are combined with the above water-insoluble polymer and water.

Add and mix the soluble polymer in an appropriate ratio, and as it is,
Alternatively, these can be dissolved in an organic solvent or a mixed solvent of an organic solvent and water, and processed into a film, sheet, or '! The drug is formulated into a rod-shaped dosage form.

If desired, plasticizers, preservatives, stabilizers, lubricants, flavoring agents, etc. may be used, and sterilization may be performed if necessary.

Usually, in the case of film-like and sheet-like preparations, the thickness is 0.1 to 0.5 mm, the width is 0.5 to 3.0 mm, and the length is 1 mm.
Form into a formulation with a size of 0 to 50 mm, and in the case of a rod-shaped formulation, the diameter is 0.5 to 1.5 mm and the length is 10 to 50 mm.
It is preferable to formulate the formulation into a size of . The thus prepared preparation of the present invention is cut into an appropriate shape depending on the symptoms, site, etc., and used by inserting or pasting it into the lower part of the body.

Examples are given below to explain the method for producing the preparation of the present invention.

Example 1 30 parts of ethylcellulose, 30 parts of methylcellulose, 40 parts of hydroxypropylcellulose and 10 parts of acrinol were uniformly mixed and a rod-shaped preparation was prepared by a melt extrusion method.

Example 2 40 parts of dimethylaminoethyl methacrylate/methyl methacrylate copolymer, 40 parts of hydroquinepropylcellulose, 5 parts of tetracycline, and 2 parts of triacetin
0 parts was dissolved in 1000 parts of ethanol, and a film with a thickness of 300 μm was prepared by a casting method.

Example 3 Ethyl cellulose IOL 70 parts of polyethylene oxide and 5 parts of ibuprofen were dissolved in 1000 parts of methylene chloride, and a 17 mm 400 μm film was prepared by a casting method.

3. Effects of Light Next, the effects of the present invention were demonstrated as in the following experimental examples.

Experimental Example 1 A film containing tetracycline hydrochloride as an active ingredient by changing the blending ratio of ethyl methacrylate/trimethylammonium ethyl methacrylate copolymer, which is an insoluble polymer, and hydroxypropyl cellulose, which is a water-soluble polymer. The dissolution rate of the active ingredient from these preparations was investigated.

Experimental method Ethyl methacrylate/trimedelammonium chloride ethyl methacrylate copolymer (molar ratio 1:20), hydroxypropyl cellulose (2% aqueous solution, viscosity 1000-4000 at 20°C), and tetrazycline hydrochloride are shown in Table 1. A film with a thickness of 200μ was prepared containing the following:

Table 1 * Units are parts by weight Elution test Cut each film shown in Table 1 into a size of 1 x 1 cz,
500 pI (7,2 phosphate buffer) at 7 °C.
The dissolution state of the drug was examined by the J, P, X rotating basket method using m(l).The properties of the film during the test period were also evaluated.

The results of the Shushi experiment are shown in Figure 1. FIG. 1 is a graph in which the horizontal axis shows the immersion time in a phosphate buffer and the vertical axis shows the drug dissolution rate, and the numbers in the figure represent sample numbers.

Samples 3 to G exhibited the characteristic softening or kelp-like properties immediately after the start of the test. Samples 7 and 8 did not soften during the test period.

The following results show that a preparation consisting of a water-insoluble polymer and a water-soluble polymer in an appropriate ratio has properties that combine the characteristics of both insoluble and water-soluble polymers.

Experimental Example 2 Samples 1 and 5 prepared in Experimental Example 1 were tested in a periodontal disease induction model (
The saw was inserted into the periodontal bulge of dogs (dogs) to compare drug residual properties.

Shoshakata-Tues f! Samples 1 and 5 adjusted to a thickness of 1 x 2 mm were administered to the 144-circumferential bulge □ (i chestnut size 4 mm) of a J disease 1 outstanding model (dog), and the residual state of the drug in the periodontal pocket was determined. was evaluated.

result The results obtained are shown in Table 2.

Table 2 +: Detected.

1: Not detected.

The above results indicate that a preparation containing an appropriate ratio of water-insoluble polymer and water-soluble polymer can remain locally for a long time and leave the active ingredient, that is, it has an excellent sustained drug release effect. This indicates that the

↓ As is clear from Experimental Examples 1 and 2, the formulation of the present invention gradually releases the active ingredient over a long period of time after administration, and when inserted into the affected area, it softens significantly and has good affinity for the administration site. It is a useful therapeutic agent for periodontal disease and has the advantage of not causing discomfort such as pain to patients.

[Brief explanation of drawings]

FIG. 1 is a graph showing the elution rate of drugs from film preparations containing water-insoluble polymers and water-soluble polymers at various blending ratios. Patent applicant: Rohto Pharmaceutical Co., Ltd. Agent: Patent attorney: Toshi Maeda (1 other person) Figure 1: 1 2 3 4 5 6 7 8

Claims (1)

[Scope of Claims] 1. A sustained-release periodontal disease treatment in the form of a sheet, film, or rod made by mixing a mixture of a water-insoluble polymer and a water-soluble polymer with a substance effective for the treatment of periodontal disease and molding the mixture. agent. 2. A first method characterized in that the blending ratio of the insoluble polymer and the water-soluble polymer is in the range of 1:9 to 7:3 in terms of dry weight ratio.
The periodontal disease treatment agent described in Section 1. 3. Insoluble polymers include ethyl cellulose, cellulose acetate, methacrylic acid/methacrylic acid trimethylammonium chloride copolymer, dimethylaminoethyl methacrylate/methacrylic acid copolymer, polyvinyl acetal/dimethylamino acetate, and cellulose acetate/dibutyl hydroxypropyl ether 2. The sustained-release periodontal disease therapeutic agent according to item 1, which is selected from the following. 4. The water-soluble polymer is methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium alginate, propylene glycol alginate, pullulan, tragacanth, xanthan gum, chitosan, polyethylene oxide, polyvinylpyrrolidone, polyvinyl alcohol, 2. The periodontal disease therapeutic agent according to item 1, which is selected from polyacrylic acid, polymethacrylic acid, or salts thereof.