JP2002249424A - Composition for mouth mucoadhesive preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for a mouth mucoadhesive preparation that holds strong and sustained adhesiveness independently of existence or amount of water in the mouth mucous membrance surface and can be ideally used for mouth hygiene, prevention and treatment for mouth disease as well as for continuous application of preparations for systemic actions. SOLUTION: This composition for the mouth mucoadhesive preparation includes (A)polyisobutylene and/or polybutene, and (B)a water soluble polymer substance as main components.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an oral mucosal adhesive preparation composition having a strong adhesive force regardless of the presence or absence of moisture on the oral mucosal surface and the amount thereof.

[0002]

2. Description of the Related Art Oral mucosa is one of the most suitable sites which can be used effectively with less discomfort and release of a medicinal component by topical application in view of exhibiting therapeutic effects. Therefore, it has been attempted to attach a sustained-release preparation for treating or preventing various diseases by administering a drug into the oral cavity to the oral mucosa. As the dosage form of the preparation, films, sheets, tablets, ointments and the like are generally used.

[0003] The film and sheet types can be made thin, so that they can be easily applied and have little discomfort in the oral cavity and are excellent in use sensation, but the dose of the drug component is limited. On the other hand, ointments or tablets have the advantage that many drug components can be blended, but they have a great discomfort in the oral cavity, dissolve in a short time, and are unsuitable when sustainability is required. As described above, each type has advantages and disadvantages and is used according to the purpose of use.

[0004] However, the adhesive force of any type is greatly affected by the presence or absence of moisture on the surface of the oral mucosa, and the amount thereof, and sometimes the adhesive force is insufficient or lacks sustainability. For example, the ointment type hardly adheres when the oral mucosal surface is wet with water such as saliva, while the tablet type hardly adheres when the oral mucosal surface is dry or slightly wet. In some cases, it fell off the oral mucosa and adhered to the tongue, failing to exert its effect. Therefore, there has been a demand for an oral mucosa-adhesive preparation composition that has strong adhesion regardless of the amount of water on the surface of the oral mucosa, has little feeling of strangeness in the oral cavity, and has a good feeling of use.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in order to meet the above-mentioned demands, and adheres without being influenced by water (presence, amount) such as saliva on the surface of the oral mucosa, and maintains the adhesive force. It is an object of the present invention to provide an oral mucosa-adhesive preparation composition to be used.

[0006]

Means for Solving the Problems and Embodiments of the Invention The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, completed the present invention.

That is, according to the present invention, there is provided an oral mucosa-adhesive preparation composition comprising (A) polyisobutylene and / or polybutene and (B) a water-soluble polymer substance as a main substrate. If there is substantially no moisture on the surface,
Even if there is little water on the oral mucosal surface, (A)
The adhesive force of the component polyisobutylene or polybutene itself exerts adhesive force, while the water-soluble polymer substance (B) imparts adhesive force to the oral mucosa where water is substantially present. And an oral mucosa-adhesive preparation composition that firmly adheres to the oral mucosal surface. In addition, by blending polyethylene with the above components, the tongue of the preparation surface can be improved and the feeling of foreign substances can be reduced. When the preparation is to be removed, the preparation can be easily removed, does not remain on the mucous membrane at all, and has a good feeling of use. An object of the present invention is to provide an oral mucosa-adhesive preparation composition which is excellent and has a good feeling in use in the oral cavity.

Hereinafter, the present invention will be described in more detail.
The oral mucosa adhesion preparation composition of the present invention, as described above,
(A) polyisobutylene and / or polybutene;
It contains (B) a water-soluble polymer substance as a main base material, and more preferably contains (C) polyethylene.

The oral mucosa-adhesive preparation composition of the present invention is substantially free of water (in a state where it is so dry that the water is not clearly observable by the eyes), or has low water content on the surface of the oral mucosa even if present. In this case, polyisobutylene and / or polybutene (A) serving as a main substrate adheres to the oral mucosal surface by its own adhesive force, while substantially water is present (obviously, water is present by eyes). On the surface of the oral mucosa, the water-soluble polymer swells due to moisture such as saliva, and polyisobutylene and / or
Alternatively, it covers the polybutene (A) and adheres by its adhesive force. Further, since polyethylene (C) has an action of aggregating polyisobutylene and / or polybutene (A) and water-soluble polymer substance (B), when the present oral mucosal adhesive preparation composition is touched with the tongue, it becomes sticky. This has the effect of making the surface dry without any blemishes, and can be easily removed when removing the present oral mucosa-adhesive preparation composition, does not remain on the mucous membrane at all, and has a good feeling in use.

[0010] Here, polyisobutylene and polybutene are represented by the average molecular weight described in the official food additive standard, and polyisobutylene has an average molecular weight of 8,700 to
200,000, preferably 8,700-60,
000 is good. If the average molecular weight is more than 200,000, it may become hard. When the average molecular weight is less than 8,700, it is used as polybutene because the polybutene is classified from the average molecular weight.

Polybutene has an average molecular weight of 500-8,
700 can be used. One type of polyisobutylene and polybutene can be used alone, and polyisobutylene and polybutene may be combined. Further, two or more types of polyisobutylene having different average molecular weights may be combined, or two types having different average molecular weights may be used. The above polybutenes may be combined.

The blending amount of polyisobutylene and polybutene is preferably 1 to 70% (mass percentage, the same applies hereinafter), particularly 10 to 35% of the whole composition. I do. In addition, adhesion to the oral mucosa when moisture is low is reduced. If the amount is too large, the amount of the water-soluble polymer substance is reduced, so that when the oral mucosa contains a large amount of water, there is a possibility that there is a disadvantage that the adhesiveness is insufficient and the adhesive may come off.

The water-soluble polymer used in the present invention may be a natural, synthetic or semi-synthetic polymer as long as it can be used in the oral cavity. Further, it may be crosslinked or non-crosslinked. For example, glucomannan, karaya gum, arabia gum, tragacanth gum, tamarind gum, locust bean gum, guar gum, xanthan gum, gellan gum, carrageenan, naturally derived water-soluble polymers such as gelatin, pectin, alginic acid salt or propylene glycol ester, carboxymethyl cellulose sodium , Metal salts of polyacrylic acid, polyethylene oxide, polyvinyl alcohol,
Polyvinyl pyrrolidone, lower alkyl vinyl ether /
Water-soluble polymers such as maleic anhydride copolymers and derivatives thereof can be given.

[0014] The content of these water-soluble polymer substances is preferably 5 to 50%, particularly preferably 20 to 40% of the whole composition. If the amount is too small, when a large amount of water exists on the surface of the oral mucosa, Insufficient adhesion may result in detachment. If the adhesion is too large, dissolution is quick and durability is reduced. In addition, there is a possibility that a disadvantage that adhesion when the amount of water is low on the oral mucosa is reduced is caused.

Polyethylene has an average molecular weight of 500 to 38,
000 is preferred. If it is larger than 38,000, it may be hard in terms of softening point and viscosity. The compounding amount is preferably 0.1 to 30%, particularly preferably 5 to 20% of the whole composition.

In the present invention, a medicinal ingredient can be blended. The oral mucosa-adhesive preparation composition of the present invention can be used in the same manner as known oral mucosa-adhesives, oral mucosal patches, and oral mucosa-adaptive preparations. However, it is preferable to prepare a non-aqueous ointment by kneading liquid paraffin or the like and the above components.

The above-mentioned medicinal components are not particularly restricted but include, for example, copper compounds such as sodium copper chlorophyllin and copper gluconate, components for preventing bad breath such as tea polyphenols and flavonoids, cetylpyridinium chloride, chlorhexidine hydrochloride, decalinium chloride. Fungicides such as glucone, chlorhexidine acid, and isopropylmethylphenol; stomatitis components such as sicon extract and triamcinolone acetonide; and gingivitis pharmacological components such as cephalexin, tetracycline hydrochloride, minocycline hydrochloride, and fradiomycin.

[0018]

EFFECT OF THE INVENTION The oral mucosa adhesive preparation composition of the present invention provides a strong and persistent adhesive property regardless of the presence or absence of water on the oral mucosal surface and the amount thereof, and provides oral hygiene and prevention of oral diseases. , Treatment, and continuous administration of systemic drugs.

[0019]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In addition, the compounding amount% of each example is all the mass%.

[Example 1] Polyisobutylene (average molecular weight: 40,000) 35% Sodium carboxymethylcellulose 30% Liquid paraffin balance 100%

[Example 2] Polyisobutylene (average molecular weight: 60,000) 20% Polybutene (average molecular weight: 3,000) 30% Sodium carboxymethylcellulose 30% Liquid paraffin balance 100%

Example 3 Polybutene (average molecular weight: 3,000) 60% sodium carboxymethylcellulose 30% liquid paraffin balance 100%

[Example 4] Polyisobutylene (average molecular weight: 60,000) 40% Gellan gum 20% Polyethylene 20% Polyethylene glycol Balance 100%

[Test Method] (1) Adhesion to oral mucosa <State where water is present on oral mucosal surface> State where saliva is sufficiently present in the oral cavity of a healthy subject and sufficient water is also present on the oral mucosal surface Then, various preparations were adhered to the buccal mucosa (first molar part) with a finger, and it was evaluated whether the preparations adhered (whether they fell without sticking).

<State where there is no moisture on the oral mucosa surface> In the mouth of a healthy person, the moisture on the oral mucosal surface is wiped using a tissue paper or the like, and then air (compressor) is immediately applied by a dental device. Keep dry. Under these conditions, the various preparations were attached to the buccal mucosa (first molars) with fingers, and it was evaluated whether the preparations adhered (whether they fell off).

<Evaluation Criteria> Δ: Sufficiently adhered (strong adhesion) Δ: Adhered but weakly adhered and moved / separated by touching with tongue or the like. ×: Does not adhere (falls)

(2) Persistence of Adhesion The oral environment (presence / absence of water) of the panel was maintained in a state suitable for adhesion of various preparations, and the preparations were adhered to the buccal mucosa (first molar part) with fingers. The persistence of adhesion of the formulation was evaluated.

<Evaluation Criteria> The time during which the adhesion was maintained was compared with that of a commercially available ointment type. ：: more than twice as long as the commercially available ointment type 〇: about 1.5 times as long as the commercially available ointment type □: having the same durability as the commercially available ointment type ×: commercially available product It is inferior in persistence to the ointment type of Comparative Example.

[0029]

[Table 1]

[0030]

[Table 2]

(3) Removability from oral mucosa Five adults without oral mucosa disease are considered to be panelists, and the oral environment (presence / absence of water) of the panelers is maintained in a state suitable for adhesion of various preparations. 5 g was attached to the buccal mucosa (first molar part) with a finger. After leaving it for 10 minutes, the preparation was removed by an arbitrary method, and the ease of removal was evaluated.

<Evaluation Criteria> The ease of removal of the preparation was absolutely evaluated in five steps.

[0033]

[Table 3]

[Procedure amendment]

[Submission date] March 2, 2001 (2001.3.2)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0015

[Correction method] Change

[Correction contents]

Polyethylene has an average molecular weight of 500 to 38,
000 is preferred. If it is larger than 38,000, it may become hard in terms of softening point and viscosity. The compounding amount is preferably 0.1 to 30%, particularly preferably 5 to 20% of the whole composition.

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0017

[Correction method] Change

[Correction contents]

The above-mentioned medicinal components are not particularly restricted but include, for example, copper compounds such as sodium copper chlorophyllin and copper gluconate, components for preventing bad breath such as tea polyphenols and flavonoids, cetylpyridinium chloride, chlorhexidine hydrochloride, decalinium chloride. Bactericides such as chlorhexidine gluconate and isopropylmethylphenol; stomatitis pharmacological components such as sicon extract and triamcinolone acetonide; and gingivitis pharmacological components such as cephalexin, tetracycline hydrochloride, minocycline hydrochloride, and fradiomycin.

Claims (2)

[Claims] 1. An oral mucosa-adhesive preparation composition comprising (A) polyisobutylene and / or polybutene and (B) a water-soluble polymer substance as main substrates. 2. The oral mucosa-adhesive preparation composition according to claim 1, further comprising (C) polyethylene.