JP2685055B2 - Oral mucosa patch containing Sikon - Google Patents

Description

TECHNICAL FIELD OF THE INVENTION The present invention relates to an oral mucosa patch containing silicon, more specifically,
The present invention relates to an intraoral preparation which is composed of a sticky layer containing silicon and a support layer that is non-adhesive to oral mucosa and can be applied to an affected part of the oral cavity to exert an anti-inflammatory effect over a long period of time.

Background Art and Problems to be Solved by the Invention Sikon (purple root) has been known as a Chinese medicine since ancient times. For example, an ointment "purple cloud plaster" was made from the extract of dried roots of purple plants, which caused skin diseases and trauma. It is often used as a medicine.

By the way, oral diseases such as alveolar pyorrhea, stomatitis,
As a treatment method for non-pain, topical administration of ointments and solutions containing various physiologically active ingredients is performed, but in this method, it is dissolved in saliva etc. in a short time after administration and swallowed, It is difficult to hold the drug in the affected area for a long time, and there is a drawback that the duration of drug effect cannot be maintained for a long time.

The present inventors have used Sicon having excellent anti-inflammatory activity, have excellent morphological stability, adherence to mucous membranes, flexibility,
As a result of intensive research to provide a novel oral mucous membrane patch with excellent drug efficacy persistence, in a formulation consisting of an adhesive layer of a specific component and a non-adhesive support layer, if the adhesive layer contains Sikon extract, The inventors have found that the target oral patch can be obtained, and have completed the present invention.

Structure and Effect of the Invention That is, the present invention comprises an adhesive layer composed of cellulose lower alkyl ethers, polyacrylic acid or a pharmaceutically acceptable salt thereof and triethyl citrate, and a water-insoluble or water-swellable polymer substance. It is intended to provide a shicon-containing oral mucous membrane patch which comprises a non-adhesive support layer and contains shikon extract as a physiologically active ingredient in the adhesive layer.

The adhesive layer in the present invention is a film-like silicon-containing layer capable of adhering to the oral mucosa and applies a drug to the affected area. Examples of the cellulose lower alkyl ethers used here include methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate and the like, and at least one of them is used (particularly, Ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate succinate are preferred). Examples of the pharmaceutically acceptable salt of polyacrylic acid include alkali metal salts such as sodium salt and potassium salt, and ammonium salt.

Such an adhesive layer generally contains 5 to 70% (lower percent by weight) of cellulose lower alkyl ethers (preferably 10 to 60%) in dry weight, in consideration of adhesion to the oral mucosa, film strength or flexibility. And polyacrylic acid or a pharmaceutically acceptable salt thereof 10 to 90% (preferably 20%)
~ 85%), which contains 5-30% plasticizer triethyl citrate and 0.5-10% shikon extract. In addition to the above, appropriate amounts of usual excipients, coloring agents, flavoring agents, flavoring agents and the like may be added.

In addition, in such an adhesive layer, it is recognized that the combination of polyacrylic acid and a water-soluble polymer substance such as aminoalkyl methacrylate or polyvinyl alcohol is inferior in adhesiveness (pasting property) (Comparative Examples 1 and 2 below). reference).

The non-adhesive support layer in the present invention is a flexible film-like layer, and imparts flexibility and drug effect durability. Examples of the water-insoluble or water-swellable polymer substance as a main component include, for example, cellulose lower alkyl ethers (ethyl cellulose, hydroxypropylmethyl cellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, carboxymethyl cellulose, carboxymethyl ethyl cellulose, etc.), sierracs, polyvinyl acetals. , Diethylaminoacetate, methacrylic acid copolymer, at least one of which
A seed is used and provided (in particular, ethylcellulose and hydroxypropylmethylcellulose acetate succinate are preferable). In addition to this, the plasticizers and other compounding ingredients exemplified in the above-mentioned adhesive layer may be used in appropriate amounts.

The oral mucosa patch according to the present invention has a film laminate layer of the above-mentioned silicon-containing adhesive layer and non-adhesive support layer formed according to a conventional method, having an appropriate shape (circular, elliptical, rectangular).
It is obtained by punching. Generally, the thickness of each layer may be selected as an adhesive layer of 50 to 150 μm and a support layer of 20 to 50 μm.

The patch of the present invention thus obtained is provided, for example, as a circular piece having a diameter of 5 to 15 mm and a total thickness of 70 to 200 μm, and therefore can be very suitable for application in the oral cavity.
It can be said that the demand is extremely high. Moreover, the following advantages can be achieved in terms of its medicinal effect and the like.

1. It firmly adheres to the oral mucosa for a long time and exerts an anti-inflammatory effect directly and accurately on the affected area.

2. It keeps the swollen form for a relatively long time without dissolving and flowing out in the oral cavity.

3. A desired drug concentration can be obtained by changing the silicon content in the preparation, and a desired drug amount can be easily obtained even if the thickness or the adhesion area is changed.

Next, the present invention will be described more specifically with reference to examples and comparative examples. The present invention is not limited to these examples.

Reference example 0.6 g of ethyl cellulose, 5 g of polyacrylic acid and 0.6 g of glycerin fatty acid ester are kneaded in 40 g of ethanol to form a paste, 0.1 g of shikon extract is added, and kneaded again to make a paper with a thickness of 70 μm. Spread on a separator and dry to form an adhesive layer containing silicon.

Further, an ethanol solution of ethyl cellulose and castor oil was evenly applied to one surface of the adhesive layer so as to have a thickness of 30 μm and dried to form a non-adhesive support layer to obtain a film laminate layer having a two-layer structure. Punching into a circle with a diameter of 10 mm gives an oral mucosa patch.

Example 1 In Reference Example, 0.6 g of ethyl cellulose, 5 g of hydroxypropylmethyl cellulose acetate succinate,
2.5 g of polyacrylic acid and 2 g of triethyl citrate in 30 g of ethanol were stirred and kneaded, and then a film-laminated layer was formed in the same manner except that a shikon-containing pressure-sensitive adhesive layer was formed using a mixture containing 0.2 g of shikon extract and then punched. Then, an oral mucosa patch is obtained.

Example 2 0.6 g of ethyl cellulose and 2 g of triethyl citrate were dissolved in 70 g of ethanol, 2.5 g of hydroxypropylmethyl cellulose, 5 g of polyacrylic acid and 10 g of water were added,
After kneading to form a paste, 0.15 g of shikon extract is added and kneaded again, and this is uniformly applied to a thickness of 70 μm and dried to form a shikon-containing adhesive layer.

Further, an ethanol solution of ethyl cellulose, hydroxypropylmethyl cellulose acetate succinate and glycerin fatty acid ester was spread on one surface of the adhesive layer to a thickness of 30 μm and dried to form a non-adhesive support layer, and a two-layer structure was formed. A film laminate layer is obtained and then punched into a circle having a diameter of 10 mm to obtain an oral mucosa patch.

Comparative Example 1 3 g of an aminoalkyl methacrylate copolymer, 4 g of polyacrylic acid and 3 g of polyethylene glycol were dispersed in 20 g of ethanol, 50 g of water was added to form a paste, and 0.2 g of shikon extract was added, followed by the same procedure as in the following reference example. A containing adhesive layer is formed, then a film laminate layer is formed, and then punching is performed to obtain an oral mucosa patch.

Comparative Example 2 5 g of polyacrylic acid and 3 g of polyethylene glycol were mixed in 15 g of ethanol, 50 g of an aqueous solution of 6 g of polyvinyl alcohol and 0.25 g of shikon extract were added, and a sticky layer containing shikon was formed in the same manner as in Example 1. Further, an oral mucosal patch is obtained by forming a film laminate layer and then punching in the same manner except that the punched shape is an elliptical shape having a major axis of 18 mm and a minor axis of 6 mm.

The following experiments were conducted for these patches to show their characteristic properties as a model.

Experiment 1 (Adhesion test) 8 patches of each patch were applied to the sides of the beaker containing 0.1M-phosphate buffer solution (pH 7.4), and the mixture was stirred with a magnetic stirrer at 200 rpm. Until the time passed, the dropout condition was observed. Table 1 shows the results.

Experiment 2 (Patch test) Each patch was stuck to the gingival mucosa of 10 volunteers, and the time until spontaneous peeling was examined. Table 2 shows the results.

Experiment 3 (Vascular hyperpermeability inhibition test) 1% Ev under light anesthesia using a hamster as an experimental animal
An's blue is administered intravenously (0.5m / 100Bu), the right cheek pouch is immediately exposed by inversion, and the cheek pouch mucosa is stimulated with xylene-impregnated felt with a diameter of 10 mm for 30 seconds, and then the test sample is applied (application time Is 1 hour and 2 hours). After the lapse of a predetermined time, the right cheek pouch was cut out together with the skin, the major axis and the minor axis of the blue dyed portion were measured, and the product (mm ² ) was used as an index.
Table 3 shows the results.

Front Page Continuation (72) Inventor Sachi Michiko 1041-5 Sanbonmatsu, Ouchi-machi, Okawa-gun, Kagawa (56) References JP-A-56-22720 (JP, A) JP-A-56-18912 (JP, A) Special Kai 57-58613 (JP, A) Actual application 59-30662 (Act 60-143737) The microfilm (JP, U) taken from the specification and drawings attached to the application.

Claims (3)

(57) [Claims] 1. An adhesive layer comprising cellulose lower alkyl ethers, polyacrylic acid or a pharmaceutically acceptable salt thereof and triethyl citrate, and a non-adhesive support layer comprising a water-insoluble or water-swellable polymer. A shikon-containing oral mucosal patch, wherein the adhesive layer contains a shikon extract as a physiologically active ingredient. 2. The patch according to claim 1, wherein the cellulose lower alkyl ether is at least one kind of ethyl cellulose, hydroxypropylmethyl cellulose and hydroxypropylmethyl cellulose acetate succinate. 3. The water-insoluble or water-swellable polymer substance is ethyl cellulose and / or hydroxypropylmethyl cellulose acetate succinate.
Item or the patch according to Item 2.