JPH01226823A - Oral mucosa plaster containing 'shikon' - Google Patents

Abstract

PURPOSE:To provide a drug for oral cavity application, composed of a tacky adhesive layer consisting of a specific component containing extract of SHIKON (root of Lithospermum erythrorhizon) and a non-tacky substrate layer, and effective in exhibiting anti-inflammatory action over a long period when applied to the diseased part in oral cavity. CONSTITUTION:The objective plaster for the application to oral mucosa is composed of (A) a tacky adhesive layer consisting of cellulose lower alkyl ethers and a polyacrylic acid or its salt and containing SHIKON extract and (B) a non-tacky substrate layer composed of a water-insoluble or water-swelling polymeric substance (preferably ethyl cellulose or hydroxypropyl methyl cellulose acetate succinate). The tacky adhesive layer preferably contains 3-70wt.% of a cellulose lower alkyl ether, 10-90wt.% of polyacrylic acid (salt), 5-30wt.% of a plasticizer and 0.5-10wt.% of SHIKON extract. The preferable thickness of the tacky adhesive layer is 50-150mum and that of the substrate layer is 20-50mum.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention is directed to an oral mucosal patch containing Sicon, more specifically, it comprises an adhesive layer containing Sicon and a support layer that is non-adhesive to the oral mucosa, and is applied to the affected area in the oral cavity. The present invention relates to an oral preparation that can be applied to the body and exert anti-inflammatory effects for a long period of time.

Prior art and problems to be solved by the invention Shikon (purple root) has been known as a Chinese herbal medicine since ancient times.
For example, an ointment called ``Shiun-yang'' is made from the extract of the dried roots of plants in the family Murasakiceae, and is used to treat skin diseases.

It is often used as an elixir for injuries.

Incidentally, as a treatment for oral diseases such as alveolar pyorrhea, stomatitis, and toothache, topical administration of ointments and liquids containing various physiologically active ingredients is performed. It is difficult to keep the drug in the affected area for a long time because it dissolves in saliva and is swallowed.
The drawback is that the medicinal effect cannot be maintained for a long time.

The present inventors used Shikone, which has excellent anti-inflammatory activity, to
In order to provide a new oral mucosal patch with excellent morphological stability, adhesion to mucous membranes, flexibility, and long-lasting medicinal efficacy, we conducted intensive research and found that an adhesive layer of specific ingredients and a non-adhesive support were developed. The present inventors have discovered that, in a preparation consisting of layers, if the adhesive layer contains Sicon extract, an intraoral patch for the intended purpose can be obtained, and the present invention has been completed.

That is, the present invention consists of a viscous S layer made of cellulose lower alkyl ethers and polyacrylic acid or a pharmaceutically acceptable salt thereof, and a non-adhesive support layer made of a water-insoluble or water-swellable polymeric substance, The present invention provides an oral mucosa patch containing Shikon, characterized in that the adhesive layer contains Shikon extract as a physiologically active ingredient.

The adhesive layer in the present invention is a film-like silicone-containing layer capable of adhering to the oral mucosa, and applies the drug to the affected area. Examples of the cellulose low i furkyl ether used here include methyl cellulose, ethyl cellulose,
Hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, etc. (preferred). Pharmaceutically acceptable salts of polyacrylic acid include alkali metal salts such as sodium salts and potassium salts, and ammonium salts.

Such an adhesive layer is generally made of cellulose lower alkyl ether @ 5 to 70% (wt%, the same applies hereinafter) (preferably 10 to 60% by weight) during dry soot overlaying, taking into account the adhesion to the oral mucosa, film strength, flexibility, etc. %) and polyacrylic acid or a pharmaceutically acceptable salt thereof, 10-90% (preferably 20-85%), plus 5-30% of a plasticizer (phthalate esters, triacetin, propylene glycol, polyethylene glycol). , triethyl citrate, etc.) and 0.5-10% Sicon extract. In addition to these, appropriate amounts of ordinary excipients, coloring agents, flavoring agents, and flavoring agents may be added.

In addition, in such an adhesive layer, polyacrylic acid and, for example, aminoalkyl methacrylate or polyester may be used.

It is recognized that adhesion (stickability) is poor when used in combination with a water-soluble polymeric substance such as vinyl alcohol (see Comparative Example 1.2 below).

The non-adhesive support layer in the present invention is a flexible film-like layer that provides flexibility and durability of drug efficacy. The water-insoluble or water-swellable polymeric substances that are the main components are:
Examples include cellulose lower alkyl ethers (ethyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, carboxymethyl cellulose, carboxymethyl ethyl cellulose, etc.), shellac, polyvinyl acetal, diethylamino acetate, and methacrylic acid copolymers; One kind is used (Ethyl cellulose and hydroxypropyl methyl cellulose acetate succinate are particularly preferred).In addition to these, appropriate amounts of the plasticizers and other ingredients exemplified for the adhesive layer may be used.

The oral mucosa patch according to the present invention can be obtained by punching the film laminate layer of the silicone-containing adhesive layer and the non-adhesive support layer formed according to a conventional method into an appropriate shape (circular, elliptical, or inky shape). It will be done. The thickness of each layer is usually selected to be 50 to 150 μm for the adhesive layer and 1120 to 50 μm for the support.

The patch of the present invention obtained in this way is provided as a circular piece with a diameter of 5 to 15 m+ and a total thickness of 70 to 200 μm, so it is very suitable for application in the oral cavity, and its demand is high. This can be said to be extremely high. Moreover,
In terms of its medicinal efficacy, it also has the following advantages.

1. It firmly adheres to the mucous membranes of the mouth and body for a long time, and exerts an anti-inflammatory effect directly and accurately on the affected area.

2. It dissolves and flows out in the oral cavity and maintains its swollen form for a relatively long period of time.

3. Desired drug al
'f can be obtained, and even if the thickness and adhesion area are changed, the drug acid can be easily obtained in a specific bottle.

Next, the present invention will be explained in more detail with reference to Examples and Comparative Examples. Note that the present invention is not limited to these examples.

Example 1 0.6y of ethyl cellulose, 5y of polyacrylic acid and 0.62y of glycerin fatty acid ester were mixed with 40y of ethanol.
After kneading it in a paste and making it into a paste, add 0.1y of Sikon extract.
was added, kneaded again, and spread on a paper separator to a thickness of 70#n, and dried to form a silicone-containing adhesive layer.

Furthermore, an ethanol solution of ethyl cellulose and castor oil was uniformly coated on one side of this adhesive layer to a thickness of 30 μm, and dried to form a non-adhesive support layer to obtain a two-layer film laminate layer. Punch out a circle with a diameter of 10 fl and apply an oral mucosal patch.

Example 2 In IJH'DI, ethylcellulose 0.6y.

Except that 5y of hydroxypropyl methylcellulose acetate succinate, 2.5y of polyacrylic acid, and 2y of triethyl citrate were stirred and kneaded in 30y of ethanol, and then 0.2y of Siconium extract was added to form a Siconium-containing adhesive layer. Similarly, a film laminate layer is formed and then punched out to obtain an oral mucosal patch.

Example 3 Ethyl cellulose 0.6y and triethyl citrate 2
y was dissolved in 70 y of ethanol, 2.52 y of hydroxypropyl methylcellulose, 5 y of polyacrylic acid, and 10 y of water were added, kneaded to form a paste, then 0.15 y of Sicon extract was added, kneaded again, and this was thickened. 70μ
The adhesive layer is coated uniformly so as to have a thickness of m and dried to form a silicone-containing adhesive layer.

Furthermore, an ethanol solution of ethyl cellulose, hydroxypropyl methyl cellulose acetate succinate, and glycerin fatty acid ester was spread on one side of this adhesive layer to a thickness of 30 μm, and dried to form a non-adhesive support layer, resulting in a two-layer structure. A film laminate layer is obtained, and then a circular shape with a diameter of 10 U is punched out to obtain an oral mucosal patch.

Comparative Example 1 Aminoalkyl methacrylate copolymer 32, polyacrylic acid 4y, and polyethylene glycol 3y were dispersed in 20y of ethanol, 5°y of water was added to make a paste, and 0.22% of Sicon extract was added.
A silicone-containing adhesive layer is formed in the same manner as above, and then a film laminate layer is formed, followed by punching to obtain an oral mucosa patch.

Comparative Example 2 5 y of polyacrylic acid and 3 y of polyethylene glycol were mixed in 15 y of ethanol, and 6 y of polyvinyl alcohol/Lzm-al, 1J liquid soy and 0.25 y of Sicon extract were mixed.
was added and used to form a silicone-containing adhesive layer in the same manner as in Example 1, and further, the punched shape was cut into a shape with a major diameter of 18 m,
4 diameter 6! An oral mucosa patch is obtained by forming a film laminate layer and then punching out the film in the same manner, except that it is shaped into an oval shape.

The experiment described in F was conducted to model the characteristic properties of these patches.

Experiment 1 (adhesion test) Eight sheets of each patch were pasted on the side of a beaker containing 0.1M phosphate buffer solution (pH 7,4), and the mixture was stirred with a magnetic stirrer at 20 orpm. The state of shedding was observed until 5 hours later. The results are shown in Table 1.

Table” (n=8) Experiment 2 (
Patch Test) Each patch was applied to the gingival mucosa of 10 volunteers, and the time required for it to peel off naturally was determined. The results are shown in Table 2.

Table 2 (.=10) Experiment 3 (vascular hyperpermeability suppression test) Using hamsters as experimental animals, 1% Ev was used under light anesthesia.
an's blue administered intravenously (Q, 5 m
/100Bu) L, immediately invert and expose the right side bag,
After agitating the mucous membrane for 30 seconds with a xylene-impregnated felt having a diameter of 10 m, the test sample is applied (application times are 1 hour and 2 hours). After a predetermined time period i, the right side pouch was cut out together with the skin, the long axis and short axis of the blue-stained part were measured, and the product (-) was used as an index. The results are shown in Table 3.

Table 3 Note ■) Same as Example 3 with Shicon extract removed.

■) Ointment containing the same amount of Sicon extract as in Example 3.

Patent applicant Teikoku Seiyaku Co., Ltd.

Claims (1)

[Claims] 1. An adhesive layer comprising cellulose lower alkyl ethers and polyacrylic acid or a pharmaceutically acceptable salt thereof;
and a non-adhesive support layer made of a water-insoluble or water-swellable polymeric substance, and the adhesive layer contains Shicon extract as a physiologically active ingredient. 2. The patch according to claim 1, wherein the cellulose lower alkyl ether is at least one of ethylcellulose, hydroxypropylmethylcellulose, and hydroxypropylmethylcellulose acetate succinate. 3. The adhesive patch according to claim 1 or 2, wherein the water-insoluble or water-swellable polymeric substance is ethylcellulose and/or hydroxypropylmethylcellulose acetate succinate.