JPH0761936B2 - Preparation containing magnetic substance - Google Patents

Description

TECHNICAL FIELD The present invention relates to a magnetic substance-containing preparation, and more specifically, it effectively concentrates and attaches a therapeutic agent to a lesion site such as the esophagus, etc., and shows an effective therapeutic effect. The present invention relates to an orally administrable magnetic substance-containing preparation.

(Conventional Technology and Problems Thereof) Conventionally, as a method for concentrating a therapeutic agent on a lesion site in the body, a method using a magnet and a method using an adhesive substance have been known.

In the method using a magnet, a therapeutic agent and a magnetic substance are integrated into a preparation, which is injected into a vessel such as a blood vessel, and a magnetic field is externally generated at the lesion site to concentrate the preparation at a target site. This is a method of increasing the drug concentration at the lesion site.

The targeting method using this magnet is usually used for the method of injecting into the blood vessel, and when the passage speed is fast like the esophagus and the distance between the inside and the outside of the esophagus is relatively large, the magnetic force There is a problem that a strong magnetic field must be generated to keep the drug at the target site with only
Conventionally, no use example is known. Further, even if it is used, there is a problem that the action of the patient is extremely limited because the strong magnetic force generator is used.

On the other hand, although a formulation in which an adhesive substance is used for integration is also known, this method is intended for treatment of the nose, mouth, etc., and the drug is orally administered to a site with a high passage rate such as the esophagus. When administered, it is difficult to attach the drug to the target site due to the swallowing effect of the esophagus, and the adhesion occurs randomly, and it is difficult to concentrate the drug only on the target site. Therefore, the examples used so far are not known.

Therefore, an object of the present invention is to concentrate a drug on a target site even at a site having a large passage speed such as the esophagus,
It is also an object of the present invention to provide an orally administrable dosage form that can be stably adhered to a target site well.

(Means for Solving Problems) The above object is achieved by the present invention described below.

That is, the present invention is an orally administrable magnetic substance-containing preparation, which comprises a magnetic material, a physiologically active substance and an adhesive substance as essential components and has adhesiveness to a target site of the esophagus.

(Function) By integrating the three components of the magnetic material, the physiologically active substance and the adhesive substance into a dosage form, the dosage form orally administered is completely adhered to the mucous membrane by the action of the adhesive substance. Although it is not enough to do so, a certain degree of adhesion effect works, so the passing speed becomes slow compared to the case of only magnetic material,
This promotes the concentration of the magnetic force on the target site. After concentration, the drug adheres to the target site due to the adhesive substance in the dosage form, and the drug can be retained at the target site even in the absence of a magnetic field.

(Preferred Embodiment) Next, the present invention will be described in more detail with reference to preferred embodiments.

As the magnetic material used in the present invention, iron, cobalt,
Any other known magnetic material such as nickel or a compound thereof can be used in the present invention, but iron oxide is particularly preferable in that it does not adversely affect the human body.

The physiologically active substance used in the present invention is a substance that exerts some action on the human body, and is not particularly limited, and examples thereof include anti-cancer agents such as fluorouracil, bleomycin, chromomycin A-3, anticancer agents, menthol and the like. Gastrointestinal substances, gastric absorbents, timepidium bromide, benzylonium bromide, methixene hydrochloride, gastric drugs such as pipenate.

The adhesive substance used in the present invention is a substance that absorbs water or mucus on the mucous membrane of the esophagus or stomach wall and exhibits adhesiveness to the mucous membrane, and a water-soluble or water-swellable polymer substance It has the property of Examples of such adhesive substances include natural polymers, semi-synthetic polymers and synthetic polymers, and examples of natural polymers include starch, gelatin, chitosan, casein, vegetable rubber, and the like. , For example, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, cellulose derivatives such as hydroxyethyl or hydroxypropyl cellulose, chitin, hydroxy or hydroxypropyl derivatives of chitosan, and the like, and as the synthetic polymer, for example, polyvinyl alcohol,
Examples thereof include polyvinyl methyl ether, polyvinyl pyrrolidone, polyhydroxyethyl acrylate, polyhydroxyethyl methacrylate, polyacrylic amide, polyethylene oxide, and the like, and of these, hydroxypropyl cellulose is particularly preferable for the purpose of the present invention. A water-swellable polymer obtained by crosslinking a water-soluble polymer as described above is also effective. Since such a water-swellable polymer is highly hydrophilic and hardly soluble in water, the drug in the formulation is gradually released. That is, a formulation excellent in sustained release is provided.

The use ratio of the above components is not particularly limited, but when the total amount is 100 parts by weight, the magnetic material is 50 to 80% by weight, the physiologically active substance is 1 to 20% by weight, and the adhesive substance is 20 to 50% by weight. The percentage that accounts for% is good.

The magnetic substance-containing preparation of the present invention contains the above-mentioned three components as essential components, but it goes without saying that other additives such as dyes may be included.

As a method of mixing the above-mentioned components and shaping them into a fixed shape, any of the conventional shaping methods generally used in the field of pharmaceuticals can be used.

For example, when a physiologically active substance that is relatively stable to heat is used, the physiologically active substance is dissolved or dispersed in an aqueous solution of a water-soluble polymer, and the magnetic material is further dispersed in this to obtain a powder by a spray drying method or the like. When the physiologically active substance is weak to heat, the above mixed solution can be freeze-dried and, if necessary, frozen and ground to a desired size. In addition, a general shaping method such as adding water to the essential components, kneading, and extrusion granulation may be used.
Further, a method in which a magnetic material and a physiologically active substance are used as a core material, and a water-soluble polymer is used as a membrane substance to perform microcapsulation may be used.

The magnetic substance-containing preparation of the present invention as described above may have any shape, but considering the ease of oral administration and the like, particles having a particle size of about 10 to 100 mesh, preferably about 20 to 50 mesh, are adhesive and stable. It is preferable in terms of release property.

(Effects) According to the present invention as described above, an orally administered formulation is prepared by combining three components of a magnetic material, a physiologically active substance and an adhesive substance into a formulation. Although it does not completely adhere to the mucous membrane due to the action, a certain degree of adhesion effect works, so the passage speed is slower than in the case of using only magnetic material, which promotes concentration of magnetic force on the target site. To be done. After concentration, the drug adheres to the target site due to the adhesive substance in the preparation, and the drug can be retained at the target site even in the absence of a magnetic field.

(Example) Next, an Example is given and this invention is demonstrated still more concretely.
In addition, unless otherwise specified, "parts" and "%" in the text are based on weight.

Example 1 Brilliant Blue FCF (BB) 10 was used as a model drug.
% Uracil mixed with γ-iron oxide, model drug and hydroxypropylcellulose in a weight ratio of 10: 1: 9
Were mixed in the ratio. A small amount of water was added to this mixture, and the mixture was further mixed, extruded from the pores to form granules, and dried under reduced pressure to obtain the magnetic substance-containing preparation of the present invention.

On the other hand, an esophageal model 1 (cylindrical body formed from an agar gel containing physiological saline) shown in FIG. 1 was prepared, and the clip 2 was first closed to prepare the above-mentioned granular magnetic substance-containing preparation. A fixed amount of the mixture was placed in a glass funnel 3, water was added, the clip was loosened, and water and granules were allowed to flow down. As a result, most of the granules are attached to the part where the magnet 4 is installed, and
The granules once attached remained attached even after the magnet 4 was removed.

Further, even if water was intermittently flown down from the glass funnel, almost no fall of the granules was observed, but it was confirmed that BB exuded from the adhered part and was gradually released.

Example 2 The same operation was carried out by replacing uracil of Example 1 with bleomycin, menthol, and timepidium bromide, respectively.

The adhesiveness of the granules was not essentially affected by the difference in the drug, and the same adhesive behavior as in Example 1 was exhibited, which was sufficient for the purpose of the present invention.

Example 3 Hydroxypropyl cellulose of Example 1 was converted from carboxymethyl cellulose Na salt, carrageenan, polyacrylic acid.
When the same experiment as in Example 1 was conducted instead of the Na salt, the adhesiveness hardly changed at all, but the sustained release property as seen from the dissolution rate of BB was best in the case of carboxymethylcellulose Na salt, In the case of carrageenan and Na salt of polyacrylic acid, the degree was almost the same.

Example 4 70 parts of iron black powder, 29 parts of low viscosity polyacrylic acid Na salt, uracil
After thoroughly mixing 0.9 parts and BB 0.1 part in a mortar, Example 1
The same operation was performed.

The initial adhesion by the magnet was good, but the sustained release rate was about twice as fast as in Example 1.

[Brief description of drawings]

FIG. 1 is a view for explaining the action and effect of the magnetic substance-containing preparation of the present invention. 1: Esophageal model, 2: Clip 3: Glass funnel, 4: Magnet

Claims (6)

[Claims] 1. An orally administrable magnetic substance-containing preparation, which comprises a magnetic material, a physiologically active substance and an adhesive substance as essential components and has adhesiveness to a target site of the esophagus. 2. The preparation according to claim 1, wherein the magnetic material is iron, cobalt, nickel or a compound thereof. 3. The preparation according to claim 1, wherein the magnetic material is iron oxide. 4. The preparation according to claim 1, wherein the physiologically active substance is a therapeutic drug. 5. The preparation according to claim 1, wherein the physiologically active substance is an antitumor agent or an anticancer agent. 6. The preparation according to claim 1, wherein the adhesive substance is a water-soluble polymer.