JPS58174307A - Edible drug for attaching to oral cavity - Google Patents

Abstract

PURPOSE:To provide an edible drug for attaching to the oral cavity, releasing the drug component to the body for a long period, and safe to swallowing, by applying a drug layer to or embedding in a substrate composed of a specific edible polymer such as a cellulose derivative. CONSTITUTION:A drug layer (preferably having a thickness of about 50-2,000mu) is applied to or embedded in substrate (preferably having a thickness of about 50-200mu) composed of one or more edible polymers such as cellulose acetate phthalate, cellulose acetate succinate, starch acetate phthalate, polyvinyl alcohol phthalate, styrene-meleic acid copolymer, etc. to obtain the objective edible drug for attaching to the oral cavity. The drug layer and the substrate are integrated together in dried state. The drug is those suitable for the absorption through the oral mucosa, e.g. remedy for pyorrhea, toothache, etc. and sublingual tablet for the fit of stenocardia.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an edible oral patch, and more particularly to an edible oral patch comprising a drug layer coated or embedded on a support mainly made of an edible specific polymeric substance. .

Drugs are administered by oral administration, injection, rectal administration (for example, herbal medicines), and troches, buccal preparations, and the like are used for the purpose of drug absorption through the oral mucosa. These lozenges are mainly used to locally act on lesions in the oral cavity, while buccal tablets are intended to gradually absorb the drug through the oral mucosa and have a systemic effect. Since the retention time is relatively short, it cannot always be said to be sufficient in terms of the amount of drug absorbed. Therefore, it has been proposed to change the patch, which is conventionally applied to the skin and used to allow certain drugs to be absorbed transdermally, into an oral patch that is applied to the oral cavity. Since this oral patch can be maintained in the oral cavity for a relatively long period of time, it is effective not only as a local agent for oral diseases but also for achieving systemic effects through mucosal absorption of the drug. However, unlike skin patches, such oral patches have drawbacks such as the drug layer disintegrating or the patch itself peeling off due to the action of saliva in the oral cavity. For this reason, waterproof non-woven fabric or paper has been proposed as a support, but if such supports are used, they may come off during sleep and be swallowed unconsciously, which poses safety problems. be.

As a result of extensive research into creating an intraoral patch that does not have these drawbacks, the present inventor has found that it can be applied to the oral cavity for a long period of time by using a support mainly made of a specific edible polymeric substance. We have now completed the present invention by discovering that it is possible to replace the oral patch medicine with sufficient safety.

According to the present invention, a cellulose derivative, a derivative of starch/sugar or a polyhydric alcohol, a tribasic acid monoester of polyvinyl alcohol or its derivative, a maleic acid copolymer, and an acrylic acid copolymer are selected from A desired edible oral patch drug can be obtained by applying or embedding a drug layer on a support mainly composed of one or more drugs to form a laminated structure.

Cellulose derivatives used in this support layer include cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, cellulose benzoate phthalate, methyl cellulose phthalate, ethyl hydroxyethyl cellulose phthalate, hydroxypropyl methyl cellulose phthalate, carboxyl methyl ethyl cellulose, etc.; starch;・Sugar or polyhydric alcohol derivatives include starch acetate phthalate, amylose acetate phthalate, etc. Dibasic acid monoesters of polyvinyl alcohol or its derivatives include polyvinyl alcohol phthalate; Maleic acid copolymers include styrene-maleic acid. Copolymers, etc.; Examples of acrylic acid copolymers include methyl acrylate-methacrylic acid copolymers, methyl acrylate-methacrylic acid-methyl methacrylate copolymers, and methyl methacrylate-methacrylic acid copolymers. There are many things that can be mentioned.

A support composition is prepared by dissolving these edible polymeric substances in water, and this is cast onto a flat plate 1 and dried to form a film as described later, or is sprayed onto a drug layer. A support is formed by coating. The ratio of this polymeric substance to water is not particularly limited, but usually about 10 to 500 parts by weight of water is used per 100 parts by weight of the polymer. In addition, this support composition contains a small amount (usually about 1 to 20% by weight based on the total weight of the support composition) of other additives,
For example, it is preferable to add glycols such as polyethylene glycol and polypropylene glycol, and inorganic fillers such as talc, bentonite, and kaolin to adjust strength such as flexibility and abrasion resistance.

Drugs are prepared by kneading the desired drug with appropriate excipients. The excipient part j includes all those used in ordinary patch medicines, but from the viewpoint of edibility, water-soluble polymer compounds such as gelatin, polyvinyl alcohol, ethyl cellulose, and carboquine methylcellulose, glycerin, propylene glycol, and sorbitol are used. Examples include polyhydric alcohols. A combination of 72 or more of these excipients is added to water with the drug under heating.
Although the amount of Ifj is not particularly limited by kneading,
Usually, 100 parts by weight of the polymer compound Δ and 10 to 1000 parts by weight of the polyhydric alcohol are mixed with 10 to 100 parts by weight of water. Additionally, if desired, a small amount of a filler such as talc, kaolin, or bentonite may be added to the drug layer composition (usually 1 to 10% culm weight based on the total weight of the drug layer composition). Good too.

The drugs to be mixed include all drugs suitable for absorption through the oral mucosa, such as cef-7rexin used for alveolar pyorrhea, tetracycline hydrochloride, oxytetracycline hydrochloride, fradiomycin, α-amylase, Chloramphenicol, also used for stomatitis and toothache, shrimp dihydrocholesterin, chromium trioxide, trigammacinolone 7cetonide, voltaren, 7nestedin,
Sodium salicylate 11um, aspirin, quinlocaine,
Examples include solcoseryl. In addition, ilnitrochrycerin is also used as a sublingual tablet during angina attacks, but is not limited to these11, 4.The amount of the drug to be added depends on the type of drug and the desired effect. In order to produce the oral patch of the present invention, it is generally selected from the range of 0.1 to 10% by weight, preferably 1 to 5% by weight, based on the total weight of the formulation for cloudiness, although it differs depending on the situation. The above composition for a support is cast onto a flat flat plate-L such as a glass plate, and dried to form a film (thickness: about 50 to 200μ in dry state, preferably about 80 to 120μ), and then attached. As shown in FIG. 1, the drug layer composition is spread and coated on this support film (1) and dried to form a drug layer (2).
Thickness of drug layer: about 50-2000μ in dry state, preferably 200-1000μ). The thus obtained laminate is cut into a desired size to make a patch. Before and after cutting, preferably, a protective film (3) of polyethylene film or cellophane film is placed on the drug layer. After pasting and use, apply this protective film inside the mouth. Alternatively, the drug layer composition is spread on a flat plate, cut into pieces of desired size, and as shown in FIG. The drug layer is coated with the support layer (1) by spraying or on a cloth, and then dried to form a patch. In the patch thus obtained, the drug layer (2) is the support layer (1).
), but the surface of the drug layer is exposed, so that when the patch is applied to the oral cavity, the drug layer comes into direct contact with the oral mucosa. In addition, even in the patch obtained by this latter method, the thickness of the support layer and drug layer is within the same range as in the former method, and a protective film is similarly pasted on the drug layer. Let it fade.

] - The edible oral patch obtained as described in 1 above can be applied to the mucous membranes in the oral cavity and retain an effective amount of the drug for a long time without being destroyed by saliva. It can be absorbed into the body and exert the desired medicinal effect. Moreover, it is extremely safe, showing no harmful effects even if swallowed during or after use.

The present invention will now be described in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 Composition for support: Ingredients Parts by weight Eudragisoto l-30D-55100 (Polymeth 7
+; Water-based acrylic resin V-reduced with − and − addition of phosphoric acid + polymethacrylic acid ester (＼Bolier lower 1.Nk Nokol (molecular weight 6000)
5 talc 10 purified y, k 1501゛, the listed ingredients, iN,', l to obtain a uniform paste.

Drug-related female.

Gelatin 20 Polyvinyl alcohol 40 Ethyl cellulose 20 Carboxymethyl cellulose 20 Glycerin
50 pro power in
3.Purified Water Put the ingredients listed in 1501 into a Neigu, heat to about 50°C, mix and dissolve with stirring to obtain a uniform liquid composition.

The above support composition is cast onto a glass plate and dried to obtain a support film (thickness: about 100 μm).

Second, the drug layer composition is spread to a thickness of about 500μ and dried to form a drug layer (thickness=300μ).

Further, a polyethylene film is laminated onto this drug layer and cut into a predetermined size (4 cll x 1 cm) to obtain a patch.

Example 2 A drug layer composition obtained in the same manner as in Example 1 was spread to a thickness of about 500μ, and a predetermined size (4α×11) was prepared.
Cut it into a drug layer. The support composition obtained in the same manner as in Example 1 is applied to each piece of the drug layer, dried, and the drug layer is embedded in the support layer as shown in FIG. 2. Get medicine (drug layer thickness: approx. 300
μ, support layer thickness; approximately 100 μ).

42 In order to test the patch retention effect in the presence of water of the patches obtained in Examples 1 and 2, the patches were pasted on a glass plate, immersed and held in purified water at 37°C, and then Changes over time were observed. As a result, in the patch of Example 1, it was observed that the drug layer slightly dissolved and disintegrated from the cut part after 5 hours, but even after 24 hours, the patch remained adhered to the glass plate and the support・No change was observed. In addition, in the adhesive patch of Example 2, no change was observed in both the drug layer and the support layer, which remained sufficiently adhered even after 24 hours.

Example 3 Composition for support: Cellulose acetate phthalate 50 Polyvinyl alcohol 70 Polyethylene glycol (molecular weight 6000) 5 Talc
10 purified water
180 Pharmaceutical compositions: Gelatin 40 Cellulose acetate phthalate 20 Hydroxypropylcellulose 50 Calhoki dimethylcellulose 30 Glycerin
60 Cephalexin
16 Purified water
100F, the above Example 1
A support composition and a drug composition were prepared in the same manner as above, and the thickness of the support layer was determined in the same manner using these compositions.
A patch having a thickness of approximately 100μ and a drug layer thickness of approximately 300μ is obtained.

[Brief explanation of the drawing]

FIG. 1 is a schematic vertical cross-sectional view showing one specific example of the intraoral patch of the present invention, and FIG. 2 is a schematic vertical cross-sectional view of another specific example. In the figure, 1: Support layer, 2: Drug layer, 3: Protective film Patent applicant: Teikoku Seiyaku Co., Ltd. Representative: Masuri Nana Aoyama, and one other person Figure 1

Claims (3)

[Claims] (1) In a patch comprising a support layer and a drug layer, the drug layer is laminated by coating or embedding it on a support mainly made of one or more edible polymeric substances. An edible oral patch drug characterized by: (2) The edible polymer substance is a cellulose derivative, starch,
The oral patch according to item (1) above, selected from sugar or polyhydric alcohol derivatives, tribasic acid monoesters of polyvinyl alcohol or its derivatives, maleic acid copolymers, and acrylic acid copolymers. (3) Support strength Cellulose acetate phthalate, cellulose acetate succinate, cellulose 7) maleate, cellulose benzoate phthalate, methyl cellulose phthalate, ethyl hydroxyethyl cellulose phthalate, hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose,
Starch acetate phthalate, amylose acetate phthalate, polyvinyl alcohol phthalate, styrene-maleic acid copolymer, methyl acrylate-methacrylic acid copolymer, methyl acrylate-methacrylic acid-
The intraoral patch drug according to item (1) above, which mainly consists of one or more selected from methyl methacrylate copolymer and methyl methacrylate-methacrylic acid copolymer. (3) The support layer and the drug layer each have a molecular weight of about 50 to 200
The adhesive patch according to item (1) above, which is formed by laminating layers with a layer thickness of about 50 to 2,000 μ (dry state).