JPH11116485A - Sucralfate suspension preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject white preparation, containing stably dispersed sucralfate, redispersing the sucralfate by shaking even after preservation for a long period and favorable for appearance by including a water-soluble cellulosic derivative and an acid ingredient in the sucralfate. SOLUTION: This preparation contains (A) sucralfate, (B) a water-soluble cellulosic derivative (e.g. methyl cellulose) and (C) at least one acid ingredient selected from phosphoric acid and organic acids (e.g. citric acid or tartaric acid) and preferably further (D) titanium oxide. In the objective preparation, e.g. the amounts of the ingredients are preferably 0.1-50 wt./vol.% ingredient A, 0.05-10.0 wt./vol.% ingredient B, 0.05-10.0 wt./vol.% ingredient C and 0.01-10 wt./vol.% ingredient D.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a suspension preparation containing sucralfate as an active ingredient.

[0002]

2. Description of the Related Art Sucralfate (sucrose sulfate aluminum salt) has almost no acid neutralizing power, but forms an ulcer-adhering complex, protects the ulcer site by the complex, and furthermore, acid, pepsin and bile. It is a drug that is thought to exhibit anti-ulcer activity by protecting those sites from salt attack. This complex is used in an acidic environment
For example, it is a rubbery gel-like bioadhesive substance formed in the stomach, which binds to bile salts and suppresses the pepsin activity of gastric juice. This complex actually facilitates adhesion to ulcer or inflammatory mucosa.

Conventionally, a preparation containing sucralfate is:
It has been administered to patients as solids such as tablets, granules, granules or powders. However, solid preparations such as tablets and granules require a long time to disintegrate, and a certain period of time is required until a drug effect appears. On the other hand, a liquid preparation such as a suspension can be said to be an advantageous dosage form because sucralfate can rapidly coat the mucous membrane of the digestive tract.

[0004] As a suspension preparation, conventional tablets, granules and the like can be suspended in water and administered to patients. However, in many cases, it is unpleasant in taste for patients who take this formulation, and because sucralfate sediments immediately, it remains in the container at the time of ingestion, and it is difficult to take a certain amount of practical use. is not.

[0005] Attempts to produce suspension formulations containing sucralfate have been made in the past, but all have failed. The reason for this is that a suspension which remains stable for a long time could not be obtained with conventional auxiliaries. That is, in order to prepare a suspension formulation, a thickening substance is generally added as a dispersant, but sucralfate releases Al ³⁺ ions in an aqueous medium and interacts with the thickening substance. This causes a significant decrease or increase in viscosity, causing the thickener to precipitate. As a result, there was a problem that the sucralfate in the suspension rapidly settled out, forming a sticky massive precipitate, and even if the container was shaken, the sucralfate was not dispersed, making administration difficult. It is.

[0006] Recently, a sucralfate suspension containing natural gums and having improved suspension properties has been developed. For example, in Japanese Patent No. 1827191, sucralfate
Disclosed is a suspension containing 〜5% by weight of xanthan gum and 1-12.5% by weight of at least one peptizer;
JP-A-5-238938 discloses a sucralfate suspension containing natural gums, a deflocculant, and sucralfate as a pharmaceutically active substance.

However, in these suspensions, since the xanthan gum or natural gums as the auxiliary have a light brown color, the suspension of sucralfate becomes a pale yellowish white suspension derived from the auxiliary. Is not preferable in appearance.

[0008]

SUMMARY OF THE INVENTION The present invention has been made in view of such circumstances. Sucralfate is stably dispersed, and even after long-term storage, is rapidly redispersed by shaking, and the appearance is reduced. It is an object of the present invention to provide a more preferred white sucralfate suspension.

[0009]

The present inventors have conducted research on sucralfate suspension. As a result, the present inventors have added a water-soluble cellulose derivative and phosphoric acid or an organic acid to an aqueous solution containing sucralfate, and further added, if necessary, The inventor has found that by adding titanium oxide, a sucralfate suspension having excellent suspension properties and appearance can be obtained, thereby completing the present invention.

That is, the present invention provides a sucralfate suspension preparation containing sucralfate, a water-soluble cellulose derivative and at least one acid component selected from phosphoric acid and organic acids, and a sucralfate suspension further containing titanium oxide. To provide a formulation.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The sucralfate suspension preparation of the present invention (hereinafter referred to as “suspension preparation”) is prepared according to a conventional method using one of acid components selected from sucralfate, a water-soluble cellulose derivative, phosphoric acid and an organic acid. It is prepared by suspending three species (hereinafter referred to as "acid components") or, if necessary, titanium oxide in purified water.

Sucralfate, which is an active ingredient of the suspension preparation of the present invention, is an aluminum salt of sucrose sulfate, and its production method and its ulcer protecting effect are already known (JP-A-59-78116). No.).

In the present invention, the water-soluble cellulose derivative is used as a suspending aid for suspension preparations. Specific examples thereof include methylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropylcellulose. Propylmethylcellulose and the like. These can be used alone or in combination of two or more.

Further, the acid component is added as a stabilizer of the suspension preparation, and specific examples thereof include phosphoric acid, citric acid,
Tartaric acid, acetic acid and the like can be mentioned. One of these acid components may be used alone, or two or more thereof may be used in combination.

The above components are usually 0.1 to 50% w / v of sucralfate, 0.05 to 10.0% w / v% of a water-soluble cellulose derivative, and 0.05 to 0.5% of an acid component in a suspension.
10.0 w / v%, preferably 0.5 to 20 w / v% sucralfate, 0.1 to 5.0 w / v% water-soluble cellulose derivative, 0.1 to 5.0 w / v acid component. v%
It is.

[0016] On the other hand, titanium oxide is a component that is added as necessary when, for example, imparting more favorable properties such as suspendability to a suspension preparation, and the amount of titanium oxide is based on the total amount of the suspension preparation. On the other hand, it is 0.01 to 1.0 w / v%, preferably 0.01%.
~ 0.1 w / v%.

In the production of the suspension preparation of the present invention, the order of addition of each component is not particularly limited, but it is possible to add and prepare a water-soluble cellulose derivative, titanium oxide, sucralfate, and an acid component in this order. preferable. In the present invention, a dispersing agent, a flavoring agent, a preservative, and a fragrance can be added as necessary, in addition to the above components.

[0018]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention.

EXAMPLES Example 1. A suspension preparation was prepared by the following formulation and preparation method. (Blend) sucralfate 4 g sodium saccharin 0.01g Hydroxypropyl cellulose 2 g titanium dioxide 0.1 g butyl parahydroxybenzoate 0.02g tartaric acid 1 g Perfume fine amount refining water qs total amount 100mL

(Preparation Method) (1) Sucralfate is weighed out, 20 mL of purified water is added thereto, and the mixture is stirred until it becomes uniform. (2) Next, hydroxypropylcellulose, titanium oxide and butyl paraoxybenzoate were weighed and purified water 50 mL.
And stir while warming. (3) Add the suspension obtained in (2) to the suspension obtained in (1), stir vigorously, and mix uniformly. Acetic acid and a fragrance were added to this to dissolve it, and purified water was added to obtain a suspension preparation having a total amount of 100 mL.

The resulting suspension preparation is white, and sucralfate is stably dispersed in the suspension. Even after long-term storage, it is rapidly redispersed by shaking and easily taken. We were able to.

Example 2 A suspension preparation was prepared by the following formulation and preparation method. (Blend) sucralfate 10 g sodium saccharin 0.02g hydroxypropylmethylcellulose 1 g titanium oxide 0.05g parahydroxybenzoate butyl 0.01g propyl parahydroxybenzoate 0.01g-phosphate 0.6 g Perfume fine amount refining water suitable The amount the total amount 100mL

(Preparation method) Prepared according to Example 1.

The obtained suspension is white, and sucralfate is stably dispersed in the suspension. Even after long-term storage, the suspension is rapidly redispersed by shaking and easily taken. We were able to.

Example 3 A suspension preparation was prepared according to the following formulation and preparation method. (Blend) sucralfate 10 g sodium saccharin 0.02g hydroxypropylmethylcellulose 0.7 g titanium oxide 0.05g parahydroxybenzoate butyl 0.01g propyl parahydroxybenzoate 0.01g-phosphate 0.3 g Perfume fine amount refining Water qs 100ml

(Preparation method) Prepared according to Example 1.

The obtained suspension is white, and sucralfate is stably dispersed in the suspension. Even after long-term storage, it is rapidly redispersed by shaking, and is easily taken. We were able to.

Example 4. A suspension preparation was prepared according to the following formulation and preparation method. (Blend) sucralfate 5 g sodium saccharin 0.01g methylcellulose 1 g of titanium oxide 1 g parahydroxybenzoate butyl 0.02g-phosphate 0.6 g Perfume fine amount refining water qs total amount 100mL

(Preparation method) Prepared according to Example 1.

The resulting suspension is white, and sucralfate is stably dispersed in the suspension. Even after long-term storage, it is rapidly redispersed by shaking, and is easily taken. We were able to.

Example 5 A suspension preparation was prepared according to the following formulation and preparation method. (Blend) sucralfate 5 g sodium saccharin 0.01g methylcellulose 1 g of titanium oxide 0.1 g p-hydroxybenzoic acid butyl 0.02g citric acid 0.8 g Perfume fine amount refining water qs total amount 100mL

(Preparation method) Prepared according to Example 1.

The resulting suspension is white, and sucralfate is stably dispersed in the suspension. Even after long-term storage, it is rapidly redispersed by shaking, and is easily taken. did it.

Example 6 A suspension preparation was prepared according to the following formulation and preparation method. (Blend) sucralfate 5 g sodium saccharin 0.01g Hydroxypropyl cellulose 1.5 g butyl parahydroxybenzoate 0.02g tartaric acid 1 g Perfume fine amount refining water qs total amount 100ml

(Preparation method) Prepared according to Example 1.

Comparative Example 1. A suspension preparation was prepared by the following formulation and preparation method. (Blend) sucralfate 4 g sodium saccharin 0.01g Hydroxypropyl cellulose 2.5 g titanium oxide 0.1 g p-hydroxybenzoic acid butyl 0.02g Perfume fine amount refining water qs total amount 100ml

(Preparation method) Preparation was carried out according to Example 1.

Comparative Example 2. A suspension preparation was prepared by the following formulation and preparation method. (Blend) sucralfate 5 g sodium saccharin 0.01g parahydroxybenzoate butyl 0.02g-phosphate 0.6 g Perfume fine amount refining water qs total amount 100ml

(Preparation method) Prepared according to Example 1.

Comparative Example 3. A suspension preparation was prepared by the following formulation and preparation method. (Blend) sucralfate 5 g sodium saccharin 0.01g cellulose 2 g titanium dioxide 0.1 g p-hydroxybenzoic acid butyl 0.02g Perfume fine amount refining water qs total amount 100ml

(Preparation method) Prepared according to Example 1.

Test Example 1. Redispersibility test: Changes in redispersibility over time of the suspension preparations prepared in Examples 1 to 5 and Comparative Examples 1 to 3 were examined. The test is performed by placing each sample in a test tube, immediately after production, and after standing at room temperature for one day and one week, gently inverting the test tube and visually confirming whether the sample is uniformly redispersed. Was. Table 1 shows the results.

[0043]

[Table 1]

[0044]

As described above, the suspension preparation of the present invention containing sucralfate as an active ingredient is a white suspension,
It is excellent in dispersibility and redispersibility, and it is possible to redisperse sucralfate uniformly by shaking the container at the time of use, even after long-term storage, and it is much easier to take as compared to the past. Was. Therefore, the suspension preparation of the present invention can be conveniently used as a suspension-type oral drug for sucralfate. that's all

Claims (2)

[Claims] 1. A sucralfate suspension preparation comprising at least one of sucralfate, a water-soluble cellulose derivative and an acid component selected from phosphoric acid or an organic acid. 2. The sucralfate suspension preparation according to claim 1, further comprising titanium oxide.