JP2003183162A - Cimetidine oral preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an oral cimetidine preparation which is excellent in compliance and is easily taken even by a patient who can hardly take a solid drug such as tablets or granules by improving the unpleasantness in oral taking due to an unpleasant taste or irritation characteristic of cimetidine. <P>SOLUTION: This oral cimetidine preparation is in a semisolid state containing cimetidine and contains a basis to keep the semisolid state of this preparation, a high-sweetness sweetener, and a low-sweetness sweetener. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an oral preparation of cimetidine, and more particularly to an oral preparation of cimetidine in which the unpleasant taste and irritation peculiar to cimetidine are improved.

[0002]

2. Description of the Related Art With the aging of society in recent years, the number of elderly people with decreased physiological functions and elderly people suffering from senile dementia is increasing. Such elderly people often have a decreased food intake function such as chewing or swallowing, or have a disorder in the food intake function, and when oral administration is performed with a solid pharmaceutical preparation such as tablets. , It was difficult to swallow the solid pharmaceutical preparation. Also, for patients with dysphagia and children,
If the size of the solid pharmaceutical preparation is large, there is a problem that it is difficult to take.

Therefore, JP-A-9-187233 and JP-A-9-194346 disclose oral pharmaceutical preparations which are easy to take even for the elderly and patients with dysphagia. In the above-mentioned publication, based on the report that a liquid preparation having high viscosity is preferred as a dosage form of an oral pharmaceutical preparation that can be easily taken by the elderly and patients with dysphagia, the dosage form of the oral pharmaceutical preparation is a jelly form. . The jelly-like oral pharmaceutical preparation can be swallowed well when swallowed directly in the mouth, and therefore can be suitably used as one of the dosage forms for the elderly and patients with dysphagia.

Cimetidine, which is known as a gastric acid secretion inhibitor, is effective for the treatment of gastric ulcer, duodenal ulcer, acute or chronic gastritis, etc. Due to its excellent medicinal effect, it is widely used as an active ingredient for medical treatment. It is used. Cimetidine may have a peculiar unpleasant taste when taken as an oral preparation, especially as a liquid preparation. therefore,
Cimetidine preparations are mainly oral tablets,
Solid preparations such as granules are used, and liquid injections are used as parenteral preparations.

However, when the patient taking the cimetidine preparation is a child, an elderly person, or a patient with dysphagia, the solid preparation may not be used in some cases. In addition, bedridden elderly people and patients with dysphagia have difficulty in taking granules with water. Therefore, as a dosage form of an oral preparation of cimetidine, it is a dosage form other than a solid preparation such as tablets and granules and a liquid solution for oral use, and is easy to take even for children, the elderly, and patients with dysphagia. It is conceivable to use a formulation.

[0006]

However, since cimetidine has a peculiar unpleasant taste such as bitterness and irritation, it causes discomfort when the dosage form of the cimetidine preparation is orally administered in the form of jelly. I have a problem. Further, such discomfort during oral administration makes it difficult to improve the compliance of the cimetidine preparation.

The present invention has been made to solve the above problems, and its purpose is to improve the discomfort during oral administration due to the unpleasant taste and irritation peculiar to cimetidine,
An object of the present invention is to provide an oral preparation of cimetidine which is easy to take even for children and elderly people who have difficulty in taking solid preparations such as tablets and granules, and patients with dysphagia, and which is excellent in compliance.

[0008]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies in order to solve the above-mentioned problems, and as a result, made a cimetidine oral preparation containing cimetidine into a semi-solid state, and obtained a semi-solid form of the cimetidine oral preparation. By blending a state-maintaining base, a high-potency sweetener, and a low-potency sweetener, the unpleasant tastes such as bitterness and irritation peculiar to cimetidine are blocked or reduced to be taken when taken orally. The present invention was completed to find an oral formulation of cimetidine that improves feeling and is easy to take for children and elderly people, patients with dysphagia, and can be swallowed easily without taking it with water when taking the drug. Came to do.

That is, the cimetidine oral preparation of the present invention is a cimetidine-containing semi-solid state cimetidine oral preparation, wherein a base that maintains the semi-solid state of the cimetidine oral preparation, a high-potency sweetener, A low-intensity sweetener, and the content of the above-mentioned base is in the range of 1.0 × 10 ⁻³ parts by weight or more and 10 parts by weight or less with respect to 1 part by weight of cimetidine, and the high-intensity sweetener described above. Content of 2.5 × 10 ⁻⁵ parts by weight or more and 0.2 parts by weight or less relative to 1 part by weight of cimetidine, and the content of the low intensity sweetener is 1 part by weight of cimetidine. On the other hand, it is characterized by being in the range of 0.5 parts by weight or more and 100 parts by weight or less.

The cimetidine is N-cyano-N'-methyl-N "-[2-[[(5-methyl-1H-imidazol-4-yl) methyl] thio] ethyl] guanidine. The cimetidine is It is used as an active ingredient for medicine and is particularly useful as a gastric acid secretion inhibitor for treating gastric ulcer, duodenal ulcer, acute or chronic gastritis and the like.

The semisolid state of the above-mentioned oral preparation of cimetidine means that it has at least one of plasticity and elasticity and can be easily deformed by an external force.

According to the above-mentioned constitution, since the unpleasant taste and irritation peculiar to cimetidine are masked by the high-intensity sweetener or the low-sweetness sweetener, cimetidine which is felt when the oral formulation of cimetidine is taken. The bitterness, irritation, and other flavors can be blocked or reduced to improve the feeling of ingestion. In addition, the bitterness caused by the addition of the high intensity sweetener can be blocked or reduced by adding the low intensity sweetener.

Further, since the above-mentioned oral preparation of cimetidine is in a semi-solid state, it has a dosage form which is easy to take even for children, the elderly and patients with dysphagia. Also, it can be easily swallowed without taking water when taking it. Therefore, it is possible to provide a convenient cimetidine oral preparation that can be taken at any time and place.

[0014] Therefore, not only for adults, but also for the elderly, whose masticatory function and swallowing function are deteriorated, and children, who have difficulty in taking solid preparations such as tablets and granules, are sufficient for treatment. It is possible to easily administer an amount of cimetidine, and obtain an oral formulation of cimetidine which is free from discomfort during oral administration and has excellent compliance.

The content of cimetidine in the above-mentioned oral preparation of cimetidine may be any amount which is pharmaceutically effective when a predetermined amount of oral preparation of cimetidine is taken. The content of cimetidine is preferably in the range of 100 to 1000 mg with respect to the dose. More specifically, it may be 2% by weight or more and 60% by weight or less with respect to the cimetidine oral preparation.

[0016] The oral preparation of cimetidine of the present invention is the above oral preparation of cimetidine, wherein the above-mentioned cimetidine is
The above-mentioned cimetidine is characterized in that it is contained in a dispersed state.

According to the above constitution, compared to the case where cimetidine is contained in a dissolved state, it is possible to block or reduce the bitterness, irritation and other flavors of cimetidine when the oral formulation of cimetidine is taken. it can. This can improve the feeling of taking the oral formulation of cimetidine and improve the compliance.

Further, the oral preparation of cimetidine of the present invention is characterized in that, in the oral preparation of cimetidine, the sweetener having a high sweetness has a sweetness of 100 or more.

The sweetness here is a numerical representation of the relative sweetness of any sweetener Q, based on the sweetness of a 3% by weight aqueous sucrose solution. That is, when an aqueous solution having a sweetness equivalent to that of a 3% by weight sucrose aqueous solution is prepared using the sweetener Q, and the concentration of the aqueous solution of the sweetener Q at this time is q% by weight, the degree of sweetness is 3 Expressed as / q.

The high intensity sweetener has a sweetness of 1
The sweetener is 00 or more, but is not particularly limited, and specifically, aspartame, aspartame derivative, acesulfame K, saccharin, saccharin salt, sucralose, stevia extract, stevia extract derivative, thaumatin, At least one selected from the group consisting of glycyrrhizinic acid and glycyrrhizinate or a mixture of two or more thereof can be mentioned. More preferably, at least one selected from the group consisting of acesulfame K, sodium saccharin, sucralose, stevia extract, and transglycosylated stevia.
Or a mixture of two or more thereof, and more preferably at least one of saccharin sodium and acesulfame K, or a mixture of these two.

The weight ratio of cimetidine to the high intensity sweetener is not particularly limited, but in the case of high intensity sweeteners other than thaumatin, preferably 1 part by weight of cimetidine is used. And high intensity sweetener 1.0 × 10
^-3 parts by weight or more and 0.2 parts by weight or less, more preferably 5.0 × 10 ^-3 parts by weight or more and 0.1 parts by weight or less of the high intensity sweetener per 1 part by weight of cimetidine. It may be selected from within the range.

When thaumatin is used as the high intensity sweetener, the ratio of thaumatin to cimetidine may be set to 1/40 of the above weight ratio. That is, 2.5 parts by weight of thaumatin was added to 1 part by weight of cimetidine.
^-5 parts by weight or more and 5.0 × 10 ^-3 parts by weight or less, more preferably 1 part by weight of cimetidine,
1.25 × 10 ^-4 parts by weight or more of thaumatin 2.5 × 10
^-3 parts by weight or less may be selected.

The oral preparation of cimetidine of the present invention is characterized in that, in the oral preparation of cimetidine, the sweetener having a low sweetness has a sweetness within a range of 0.1 or more and 10 or less.

The low-intensity sweetener is not particularly limited as long as it has a sweetness in the range of 0.1 or more and 10 or less, and specifically, lactose, glucose and fructose. , Maltose, sucrose, trehalose, mannitol, erythritol, sorbitol, xylitol, maltitol, glycerin, reduced maltose starch syrup, powdered reduced maltose starch syrup, and a mixture of two or more thereof. More preferably, at least one kind or a mixture of two or more kinds selected from the group consisting of sucrose, sorbitol, reduced maltose starch syrup, and powdered reduced maltose starch syrup is preferable, and at least one of reduced maltose starch syrup and powdered maltose starch syrup is more preferable. Seed or mixtures of these two.

The weight ratio of cimetidine to the low intensity sweetener is not particularly limited, but is preferably
The low-sweetness sweetener is selected from the range of 0.5 parts by weight or more and 100 parts by weight or less with respect to 1 part by weight of cimetidine, and more preferably 5 parts by weight of the low-sweetness sweetener with respect to 1 part by weight of cimetidine. It may be selected from the range of 50 parts by weight or less.

The oral preparation of cimetidine of the present invention is the above oral preparation of cimetidine, wherein the semisolid state of the oral preparation of cimetidine is any one of jelly state, paste state and gummy state. I am trying.

As a base for the case where the semi-solid state is a jelly state (hereinafter referred to as a jelly base), a jelly-like composition that is edible and can be eaten and drinks and is usually used for foods, pharmaceuticals, cosmetics and the like is used. It may be used and is not particularly limited. Specifically, for example, agar, gelatin, pectin, carrageenan, locust bean gum, gellan gum, xanthan gum, guar gum, gum arabic, glucomannan, pullulan, curdlan, alginic acid, alginate, polyacrylic acid, polyacrylic acid At least one kind or a mixture of two or more kinds selected from the group consisting of solvates, polyacrylic acid salts, and partially neutralized polyacrylic acid salts.

The above carrageenan includes κ type, ι type and λ type. In the following description, when simply described as carrageenan, any of these three types may be carrageenan. Shall be indicated.

Of the above jelly bases, agar, κ-carrageenan, locust bean gum,
Gellan gum, xanthan gum, alginic acid, at least one member selected from the group consisting of alginates, or a mixture of two or more, and more preferably, at least one member selected from the group consisting of κ-carrageenan, locust bean gum, xanthan gum or Mixtures of two or more may be mentioned.

Further, the weight ratio of cimetidine to jelly base is not particularly limited, but preferably, 1 part by weight of cimetidine and 1.0 × 1 of jelly base.
It is selected from the range of 0 ^-3 parts by weight or more and 2 parts by weight or less, and more preferably the range of 5.0 × 10 ^-3 parts by weight or more and 0.5 parts by weight or less of the jelly base with respect to 1 part by weight of cimetidine. You can choose from.

Further, as a base material (hereinafter referred to as a paste base material) when the semi-solid state is a paste state, a paste-like composition which is edible and can be eaten and drink and is usually used for foods, pharmaceuticals, cosmetics and the like. May be used and is not particularly limited. Specifically, for example, gelatin,
At least one selected from the group consisting of pectin, ι-carrageenan, λ-carrageenan, locust bean gum, xanthan gum, alginic acid, alginate, carboxymethyl cellulose and carboxymethyl cellulose salt, or a mixture of two or more kinds thereof can be mentioned.

Of the above paste bases, preferably, at least one selected from the group consisting of pectin, ι-carrageenan, locust bean gum, alginic acid and alginate, or a mixture of two or more thereof, and more preferably, Pectin is mentioned.

The weight ratio of cimetidine to the paste base is not particularly limited, but preferably 1.0 part of the paste base to 1 part by weight of cimetidine.
× 10 ⁻³ parts by weight or more and 1 part by weight or less,
More preferably, it should be selected from the range of 1.0 × 10 ⁻³ parts by weight or more and 0.5 parts by weight or less of the paste base with respect to 1 part by weight of cimetidine.

Further, the base in the case where the above semi-solid state is a gummy state (hereinafter referred to as a gummy base) is edible, and has a gummy composition which is usually used for foods, pharmaceuticals, cosmetics and the like. Any material may be used and it is not particularly limited. Specific examples thereof include agar, gelatin, κ-carrageenan, ι-carrageenan, λ-carrageenan, locust bean gum, gellan gum, xanthan gum, alginic acid, and a mixture of two or more kinds of alginates. To be

Of the above gummy bases, preferably, at least one kind or a mixture of two or more kinds selected from the group consisting of gelatin, ι-carrageenan, λ-carrageenan, locust bean gum, gellan gum and xanthan gum, and further, Preferred is gelatin.

Further, the weight ratio of cimetidine and gummy base is not particularly limited, but preferably 0.1 part by weight to 10 parts by weight of gummy base per 1 part by weight of cimetidine. It may be selected from the range, and more preferably from 0.5 part by weight or more and 5 parts by weight or less of the gummy base with respect to 1 part by weight of cimetidine.

Further, the oral preparation of cimetidine of the present invention is the above-mentioned oral preparation of cimetidine, wherein the semisolid state of the oral preparation of cimetidine is jelly, and the content of the above-mentioned base is 1 part by weight of the above-mentioned cimetidine. It is characterized in that it is in the range of 0.0 × 10 ⁻³ parts by weight or more and 2 parts by weight or less.

Further, the jelly strength of the above-mentioned oral preparation of cimetidine in the jelly state is characterized by being in the range of 300 mN or more and 5000 mN or less.

The strength of the above jelly base is determined by the following measurements. First, an oral formulation of cimetidine consisting of jelly base is prepared in a 50 ml beaker, and the beaker containing the oral formulation of cimetidine in jelly state is placed on the measuring table of a small tabletop tester (EZ Test-500N, manufactured by Shimadzu Corporation). . Then, a compression jig having a diameter of 15 mm for measuring jelly strength is penetrated into the surface of the above-mentioned cimetidine oral preparation in a beaker, and 20 m from the surface of the cimetidine oral preparation.
The load at the time of m is measured and the load is taken as the jelly strength.

According to the above-mentioned constitution, since the jelly strength of the cimetidine oral preparation in the jelly state is such that the jelly strength is easy to take, the elderly person having a masticatory function and a swallowing function deteriorated, the patient with a dysphagia, Even for children who have difficulty taking solid formulations,
You can easily swallow without chewing. Also,
Even if you do not take it with water, you can swallow it easily, so you can take it at any time and place,
It is very convenient.

The oral preparation of cimetidine of the present invention is the above-mentioned oral preparation of cimetidine, wherein 1 part by weight of the oral preparation of cimetidine is dissolved or dispersed in water in the range of 2 parts by weight or more and 10 parts by weight or less and the pH is 5 or more. It is in the range of 9 or less, and more preferably in the range of 6 to 8.

According to the above constitution, the pH within the above range
By maintaining the stability of cimetidine itself, an oral preparation of cimetidine having excellent storage stability can be provided.

[0043]

BEST MODE FOR CARRYING OUT THE INVENTION An embodiment of the present invention will be described below.

The cimetidine oral preparation of the present invention is a cimetidine-containing semi-solid state cimetidine oral preparation, wherein the base maintains the semi-solid state of the cimetidine oral preparation, a high-potency sweetener and a low-sweetness sweetener. Contains sweeteners. The base, the high intensity sweetener and the low intensity sweetener are as described above, and the contents thereof are also as described above.

The cimetidine oral preparation of the present invention may further contain a gelling agent in order to promote gelation of the base material which maintains the semisolid state of the cimetidine oral preparation. As the gelling agent, an appropriate one may be selected depending on the base that maintains the semisolid state of the cimetidine oral preparation.For example, when carrageenan is used as the base, it consists of sodium chloride, potassium chloride and calcium chloride. At least one kind of the group or a mixture of two or more kinds thereof may be mentioned.

The weight ratio of cimetidine to the gelling agent may be appropriately determined according to the gelling agent. For example, when the base is carrageenan, 1 part by weight of the gelling agent to 1 part by weight of cimetidine is used. 0.0 × 10 ⁻³ parts by weight or more and 0.1 parts by weight or less, and more preferably 5.0 × 10 ⁻³ parts by weight or more and 5.0 × with respect to 1 part by weight of cimetidine.
It may be selected from the range of 10 ^-2 parts by weight or less.

Furthermore, the oral formulation of cimetidine of the present invention comprises
In order to prevent water separation from the base material and obtain storage stability, a water separation inhibitor may be included. Examples of the water separating agent include, for example, pectin, ι-carrageenan, locust bean gum, xanthan gum, polyacrylic acid, partially neutralized polyacrylic acid, polyacrylic acid salt, partially neutralized polyacrylic acid salt. At least one kind or a mixture of two or more kinds of the above.

The weight ratio of cimetidine to the water-repellent inhibitor is not particularly limited, but when the water-repellent inhibitor also serves as the base of the oral formulation of cimetidine, it is preferably 1 part by weight of cimetidine. The water separation inhibitor may be selected from the range of 1.0 × 10 ⁻³ parts by weight or more and 2 parts by weight or less, and more preferably 5.0 × 10 ⁻³ parts by weight of the water separation inhibitor with respect to 1 part by weight of cimetidine. It may be selected from the above range of 0.5 parts by weight or less.

On the other hand, the weight ratio of the water-repellent inhibitor in addition to the components contained in the base is preferably 1.0 × 10 ⁻³ parts by weight or more of the water-repellent inhibitor with respect to 1 part by weight of cimetidine. It may be selected from the range of 0.5 parts by weight or less, and more preferably from the range of 5.0 × 10 ⁻³ parts by weight or more and 0.1 parts by weight or less of the water separating agent to 1 part by weight of cimetidine. do it.

The oral preparation of cimetidine of the present invention is
To enhance the sweetness of cimetidine oral preparations, sodium chloride
It may contain helium. Cimetidine and sodium chloride
The weight ratio with the
There is no particular limitation as long as it is within the range,
Sodium chloride 1.0 × 10 to 1 part by weight of thyzine ^-2
Select from the range of not less than 0.25 parts by weight and not more than
More preferably, sodium chloride is used with respect to 1 part by weight of cimetidine.
Um 5.0 × 10^-2A range of more than or equal to 0.15 parts by weight
It is recommended to select from within the box.

Further, the oral formulation of cimetidine of the present invention comprises
A pH adjusting agent may be added to adjust the pH of the oral formulation of cimetidine and ensure the stability of cimetidine. As a pH adjuster, p which is generally used
The H-adjusting agent is not particularly limited, and examples thereof include hydrochloric acid and sodium hydroxide.

In particular, when the pH of the oral preparation of cimetidine fluctuates during storage, a buffer may be added to maintain the predetermined pH. The buffer is not particularly limited as long as it can maintain a predetermined pH, but is preferably malic acid, malate, citric acid, citrate, tartaric acid, tartrate, ascorbic acid,
Ascorbate, succinic acid, succinate, fumaric acid,
Fumarate, maleic acid, maleate, gluconic acid,
At least one or two selected from the group consisting of gluconate, glucuronic acid, glucuronic acid, phosphoric acid, and phosphate.
Mixtures of more than one species are mentioned. More preferred buffering agents include malic acid, malate, citric acid, citrate,
At least one selected from the group consisting of tartaric acid, tartaric acid salt, phosphoric acid, and phosphoric acid may be used, or a mixture of two or more may be used, and particularly preferably, at least one of malic acid and malic acid may be used. The concentration of the buffer solution is not particularly limited, but it is preferable to select it in the range of 5 mM or more and 50 mM or less.

The oral formulation of cimetidine of the present invention may contain a flavoring agent or a flavoring agent in order to improve the feeling of ingestion of the oral formulation of cimetidine. As a fragrance and flavoring agent,
It is not particularly limited as long as it is usually used,
Specifically, at least one or more selected from the group consisting of tea, coffee, green tea, peppermint, spearmint, menthol, herb, peppermint, lemon, lemon lime, grapefruit, yuzu, ume, grape, peach, yogurt. A mixture of More preferably, at least one of the group consisting of peppermint, spearmint, menthol, herbs, peppermint, lemon, lemon lime, grapefruit, plum and yogurt.
Examples include species or a mixture of two or more species.

The weight ratio of cimetidine to the flavor or fragrance is 1 part by weight of cimetidine, and the flavor or fragrance is 2.
It may be selected from the range of 0 × 10 ⁻³ parts by weight or more and 0.1 parts by weight or less, and preferably 5.0 × 10 ⁻⁴ parts by weight or more of fragrance or flavoring agent per 1 part by weight of cimetidine. It may be selected from the range of 2 parts by weight or less.

Further, the oral formulation of cimetidine of the present invention comprises
An antiseptic agent may be included in order to prevent deterioration of quality due to microorganisms and ensure good quality. The preservative is not particularly limited as long as it is a commonly used preservative, preferably methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, isopropyl paraoxybenzoate, Isobutyl paraoxybenzoate, benzoic acid, benzoate, benzyl benzoate, aminoethylsulfonic acid, ethanol, sodium edetate, dl-camphor, salicylic acid, salicylate, phenyl salicylate, dibutylhydroxytoluene, sorbic acid, sorbate, At least one selected from the group consisting of dehydroacetic acid, dehydroacetic acid salt, 2-naphthol, dl-borneol, menthol, and eucalyptus oil, or a mixture of two or more thereof may be mentioned.

The content of the preservative is as follows: Cimetidine oral preparation 1
1.0 × 10 ⁻⁴ parts by weight or more, 1.0 × 1 with respect to parts by weight
It may be selected from the range of 0 ^-3 parts by weight or less.

The oral formulation of cimetidine of the present invention may contain, in addition to the above-mentioned additives, non-toxic and inactive additives usually used in the field of formulation in any proportion. Such additives are not particularly limited as long as they do not substantially affect the cimetidine oral preparation of the present invention, but those used as pharmaceutical additives are preferable.

Specifically, corn starch, potato starch, talc, kaolin, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, excipients such as crystalline cellulose, magnesium stearate, magnesium stearate, calcium stearate and the like lubricants. Drug,
Carboxymethyl cellulose calcium, disintegrating agent such as low-substituted hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose,
Polyvinylpyrrolidone, gelatin, methylcellulose,
Examples thereof include gum arabic powder, binders such as polyvinyl alcohol, colorants, flavoring agents, adsorbents, stabilizers, wetting agents, and antistatic agents.

The oral preparation of cimetidine of the present invention can be produced by a conventionally known preparation method. Hereinafter, a preparation method using a jelly base or a paste base and a preparation method using a gummy base will be described.

First, the case where a jelly base or a paste base is used as the base will be described. An appropriate amount of purified water is added to the above-mentioned cimetidine to adjust the pH to 6 or less, and then the mixture is stirred with a stirrer to prepare a cimetidine solution in which cimetidine is dissolved in the purified water. In this cimetidine solution,
Base, high-intensity sweetener,
Add low-intensity sweetener and any of the other additives listed above,
Further, an appropriate amount of purified water is added and stirred with a stirrer to dissolve or disperse cimetidine.

Then, the obtained dissolved or dispersed liquid is heated to a temperature at which the base is dissolved. The heating temperature at this time is
It is usually 60 to 95 ° C. When it is not preferable to heat the heating temperature to a high temperature due to volatilization of any additive such as a fragrance, the heating temperature is cooled to such an extent that the fluid state of the dissolved or dispersed liquid is maintained. After that, the above additives may be added. Further, at this time, a pH adjustor may be added so that the pH is 9 or less within the range in which cimetidine is not dissolved. As described above, since heating and cooling are carried out in the preparation of the oral preparation of cimetidine, it is preferable that the stirrer used can be temperature controlled.

Subsequently, the above-mentioned dissolved or dispersed liquid is poured into a storage container in an appropriate amount at a temperature at which the fluid state is maintained, and the solution is dispersed in an amount of 5-2.
When cooled to 5 ° C. and allowed to stand for 1 to 8 hours, the dissolved base becomes a semi-solid state, and an oral formulation of cimetidine containing the base in jelly state or paste state can be obtained.
If the temperature at which the base material dissolves is lower than room temperature,
By adding a gelling agent before injection into a storage container, an oral preparation of cimetidine in jelly state or paste state can be obtained.

Next, the case where a gummy base is used as the base will be described. An appropriate amount of purified water is added to the above-mentioned base to swell it, and then the base is dissolved by heating. Here, a low-intensity sweetener is added so as to have the above-mentioned content. The low-intensity sweetener added at this time is dissolved in an appropriate amount of purified water in advance, further heated and boiled down.

Subsequently, an appropriate amount of purified water is further added to the solution prepared by adding the low-intensity sweetener to the base, and the high-intensity sweetener and any of the above-mentioned additives are added so that the above-mentioned content is obtained. And stir with a stirrer. A gummy dough is obtained by this stirring. Then, finely divided cimetidine is added and mixed at a temperature at which the gummy dough does not solidify. further,
Gummy dough containing cimetidine is divided into appropriate sizes, cooled to 5 to 25 ° C., and left for 1 to 24 hours, the gummy dough becomes a semi-solid state, and a gummy state cimetidine oral preparation can be obtained. .

[0065]

EXAMPLES Examples of the present invention will be described below.
The present invention is not limited to this.

[Examples 1 and 2] Ingredient A in Table 1 was weighed out, cimetidine was dissolved in purified water, and the hydrochloric acid shown in Table 1 was added to adjust the pH to about 6. To this solution, Table 1
After dissolving or dispersing component B of Example 1 and heating to 95 ° C., further adding component C of Table 1 and cooling, an oral preparation of cimetidine in jelly state was obtained. Amarti MR (registered trademark, manufactured by Towa Kasei Kogyo Co., Ltd.) was used as the powdered maltose starch syrup in the table.

[0067]

[Table 1]

[Examples 3 and 4] Component B in Table 2 was weighed out, and this component B was mixed and dispersed, and further heated to prepare a solution in which component B was dissolved. The solution was cooled at room temperature and when the temperature was cooled to 55-60 ° C.
The pH was adjusted to about 7 by adding the hydrochloric acid shown in Table 2, and the component C in Table 2 was
Was added. Then, when the temperature reaches 50 ° C,
Component A in Table 2 was added and dispersed to obtain a cimetidine oral preparation in a jelly state.

[0069]

[Table 2]

Example 5 The components shown in Table 3 were weighed out and dissolved in purified water. This solution was heated to dissolve or suspend each component, and then cooled to obtain a pasty cimetidine oral preparation.

[0071]

[Table 3]

Example 6 First, powdered reduced maltose starch syrup was heated to about 130 ° C. and boiled down. Also, for gelatin,
Purified water a was added to swell and heated to about 60 ° C. to dissolve gelatin. Next, dissolved gelatin was added to the above-mentioned boiled powdered reduced maltose starch syrup and mixed with stirring. Further, purified water b, sucralose and citric acid were added to obtain a gummy dough having a water content of 20%. Immediately before cooling and solidification of the gummy dough, micronized cimetidine was added and cooled to obtain a gummy-state cimetidine oral preparation. The amount of each component added is shown in Table 4.

[0073]

[Table 4]

Comparative Example Each component shown in Table 5 was weighed out and dissolved in purified water to obtain a liquid cimetidine liquid preparation.

[0075]

[Table 5]

[Evaluation of Cimetidine Oral Formulation of the Present Invention] The cimetidine oral formulations obtained in the above Examples 1 to 5 and the cimetidine liquid formulation obtained in Comparative Examples were subjected to a sensory test by three panelists. It was The sensory test was performed by evaluating the taste and the feeling of ingestion when each oral formulation of cimetidine or the liquid formulation of cimetidine was directly put into the mouth.
Here, the feeling of ingestion is an index representing ease of swallowing such as flavors other than the taste felt when the oral formulation of cimetidine or the liquid formulation of cimetidine is taken directly into the mouth, ease of swallowing, and the like. The results are shown in Table 6.

The evaluation criteria are as follows. (Evaluation Criteria) ◎: No unpleasant taste is felt and the feeling of taking is good ○: No unpleasant taste is felt, and the feeling of taking is normal, or a slightly unpleasant taste is felt , If the feeling of taking is good △: Somewhat unpleasant taste is felt, and if the feeling of taking is normal ×: Very unpleasant taste is felt, and feeling of taking is poor

[0078]

[Table 6]

As shown in Table 6, when the oral administration of cimetidine is orally administered, the feeling of ingestion is improved as compared with the case where the cimetidine solution is orally administered. Especially when the cimetidine oral preparation is in the jelly state,
It can be seen that an oral formulation of cimetidine that can be easily taken without providing an unpleasant taste can be provided.

[0080]

As described above, the oral preparation of cimetidine of the present invention comprises a base material which maintains the semisolid state of the oral preparation of cimetidine, a high-potency sweetener and a low-sweetness sweetener in a predetermined ratio. It is one that includes.

Therefore, the unpleasant taste such as bitterness and irritation peculiar to cimetidine can be blocked or reduced to improve the feeling of oral administration, and also for children, the elderly and patients with dysphagia. The effect is that it is easy to take, and can be swallowed easily without taking it with water when taking it.

Therefore, not only for adults, but also for the elderly, whose masticatory function and swallowing function are deteriorated, and for children, who have difficulty in taking solid preparations such as tablets and granules, are sufficient for treatment. The effect that the amount of cimetidine can be easily taken and an oral formulation of cimetidine excellent in compliance can be obtained.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 47/26 A61K 47/26 47/32 47/32 47/36 47/36 47/42 47/42 A61P 1/04 A61P 1/04 (72) Inventor Hirohisa Kobayashi 1-345 Kuragakiuchi, Ibaraki-shi, Osaka Sumitomo Pharmaceutical Co., Ltd. F-term (reference) 4C076 AA09 BB01 CC16 DD38 DD51 DD61 DD67 DD69 EE09 EE30 EE36 EE42 EE58 FF35 FF52 4C086 AA01 AA02 BC38 MA03 MA05 MA21 MA28 MA52 NA09 ZA68

Claims (12)

[Claims] 1. A semi-solid state oral formulation of cimetidine containing cimetidine, which comprises a base for maintaining the semi-solid state of the oral formulation of cimetidine,
A high-intensity sweetener and a low-intensity sweetener are included, and the content of the above-mentioned base is 1 part by weight of cimetidine.
0 × 10 ⁻³ parts by weight or more and 10 parts by weight or less,
The content of the high-potency sweetener is within the range of 2.5 × 10 ⁻⁵ parts by weight or more and 0.2 parts by weight or less relative to 1 part by weight of cimetidine, and the content of the low-potency sweetener is An oral formulation of cimetidine, characterized in that it is in the range of 0.5 parts by weight or more and 100 parts by weight or less with respect to 1 part by weight of cimetidine. 2. The oral preparation of cimetidine according to claim 1, wherein the content of cimetidine is 2% by weight or more and 60% by weight or less based on the oral preparation of cimetidine. 3. The cimetidine oral preparation according to claim 1, wherein the cimetidine is contained in a dispersed state. 4. The oral cimetidine preparation according to claim 1, 2 or 3, wherein the high-potency sweetener has a sweetness of 100 or more. 5. The high-intensity sweetener is aspartame,
Aspartame derivative, acesulfame K, saccharin, saccharin salt, sucralose, stevia extract, stevia extract derivative, thaumatin, glycyrrhizic acid,
It is a mixture of at least one kind or two or more kinds of the group consisting of glycyrrhizinate.
An oral formulation of cimetidine according to any one of claims 1 to 4. 6. The oral preparation of cimetidine according to any one of claims 1 to 5, wherein the low-intensity sweetener has a sweetness in the range of 0.1 or more and 10 or less. 7. The low intensity sweetener is lactose, glucose,
Fructose, maltose, sucrose, trehalose, mannitol, erythritol, sorbitol, xylitol, maltitol, glycerin, reduced maltose starch syrup, powdered reduced maltose starch syrup, or a mixture of two or more thereof, characterized in that The cimetidine oral preparation according to any one of claims 1 to 6. 8. The base is agar, gelatin, pectin,
Carrageenan, locust bean gum, gellan gum,
Of the group consisting of xanthan gum, guar gum, gum arabic, glucomannan, pullulan, curdlan, alginic acid, alginate, polyacrylic acid, partially neutralized polyacrylic acid, polyacrylic acid salt, partially neutralized polyacrylic acid salt 8. An oral formulation of cimetidine according to any one of claims 1 to 7, which is a mixture of at least one or two or more of 9. The semisolid state of the above oral formulation of cimetidine is
The cimetidine oral preparation according to any one of claims 1 to 8, which is in a jelly state, a paste state, or a gummy state. 10. A semisolid state of an oral formulation of cimetidine is a jelly state, and the content of the above-mentioned base is the above-mentioned cimetidine 1.
The oral formulation of cimetidine according to any one of claims 1 to 8, which is in the range of 1.0 x 10 ^-3 parts by weight or more and 2 parts by weight or less with respect to parts by weight. 11. The oral preparation of cimetidine according to claim 10, wherein the jelly strength of the oral preparation of cimetidine in jelly state is in the range of 300 mN to 5000 mN. 12. The pH of a product obtained by dissolving or dispersing 1 part by weight of the oral formulation of cimetidine in water in the range of 2 parts by weight or more and 10 parts by weight or less in the range of 5 or more and 9 or less. An oral formulation of cimetidine according to any one of 1 to 11.