JP2001064182A - Sucralfate-suspended liquid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sucralfate suspension preparation desirably white in appearance in which the sucralfate is stably dispersed in the suspension, resistant to sedimentation, readily redispersible by shaking, even when it is sedimented, can be readily taken, as giving smooth texture in the oral cavity without rough touch and sticking to mucous membrane on dosing. SOLUTION: This sucralfate suspension preparation comprises sucralfate, a water-soluble carboxy-vinyl polymer, and at least one selected from among polyphosphate salt and/or phosphoric acid and/or the salt thereof. The formulation amount of the water-soluble carboxy vinyl polymer is 0.1-2 w/v%, the amount of the polyphosphate salt and/or phosphoric acid or the salt thereof is 0.5-1 w/v% based on the whole amount of the preparation.

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 (aluminum salt of sucrose sulfate) is a drug for peptic ulcer listed in the Pharmacopoeia and has almost no acid neutralizing power, but is contained in white moss (Belague) at the bottom of the ulcer. It selectively binds to various blood-derived protein components to form an ulcer-adhering complex, and the protective layer of the ulcer-adhering complex protects the ulcer-forming part from attack by acids, pepsin and bile salts. It is a drug that is considered to exhibit anti-ulcer activity. The ulcer-adhesive complex becomes a highly adhesive gel in an acidic environment, for example, in the stomach, and forms a strong protective layer.

[0003] Conventionally, a preparation containing sucralfate has been administered to a patient as a solid preparation such as a tablet, granule or powder. However, solid preparations such as tablets and granules require a long time to disintegrate, and a certain period of time is required until the drug effect appears. In contrast, liquid formulations such as suspensions,
Sucralfate is an advantageous dosage form because it can rapidly coat the mucous membranes of the digestive tract.

[0004] Conventional tablets, granules and the like can be suspended in water and administered to patients as suspensions. However, in this case, sucralfate immediately settles out, remains in the container at the time of ingestion, and it is difficult to take a certain amount, or the suspended particles are large due to insufficient dispersibility, so that it was taken. At this time, problems occur such as roughening in the oral cavity and discomfort due to adhesion to the oral mucosa.
Therefore, it is not practical to simply use tablets and granules suspended in water.

[0005] Attempts to produce a suspension formulation containing sucralfate have been made in the past, but the above-mentioned problems have been encountered, and a satisfactory suspension formulation has not been obtained in any case. This is mainly due to the fact that long-lasting suspensions cannot be obtained with conventional auxiliaries. That is, to prepare a suspension formulation, generally,
Although a thickener is incorporated as a dispersant, sucralfate releases ^{Al3 +} ions in an aqueous medium, and causes an interaction with the thickener, resulting in a large decrease or increase in viscosity. This produces a sticky precipitate. As a result, sucralfate in the suspension rapidly precipitated to form a sticky massive precipitate, and even when the container was shaken during use, sucralfate did not disperse and was difficult to take.

[0006] Recently, a sucralfate suspension containing natural gums and having improved suspension properties has been developed. For example, in Japanese Patent Publication No. 5-35130, sucralfate contains 1 to 5% by weight of xanthan gum and 1 to 5% by weight.
Disclosed is a suspension containing 12.5% by weight of peptizer,
JP-A-5-238938 discloses a sucralfate suspension containing natural gums, a deflocculant and sucralfate as a pharmacologically active substance. Japanese Patent Application Laid-Open No. H11-116485 discloses a sucralfate suspension formulation containing a water-soluble cellulose derivative, phosphoric acid, an organic acid, and titanium oxide.

However, these suspensions are pale yellowish white suspensions derived from the auxiliary, because xanthan gum or natural gums as the auxiliary have a light brown color. In addition, most of the water-soluble cellulose derivatives have a slightly yellowish white color, and titanium oxide is blended in order to adjust the appearance.

[0008]

SUMMARY OF THE INVENTION The present invention has been made in view of such circumstances. Sucralfate is stably dispersed and hardly sedimented, or rapidly redispersed by shaking even if it is settled. An object of the present invention is to provide a white sucralfate suspension which is easy to be taken without taking a rough appearance in the oral cavity or adhering to mucous membranes when taken, and which is preferable in appearance.

[0009]

DISCLOSURE OF THE INVENTION The present inventors have conducted various studies on sucralfate suspension, and as a result, found that a water-soluble carboxyvinyl polymer and a polyphosphate and / or phosphorus were contained in a suspension containing sucralfate. It has been found that by adding an acid or a phosphate, a sucralfate suspension having excellent suspension properties and appearance can be obtained, and the present invention has been completed.

That is, the present invention is a sucralfate suspension formulation containing sucralfate, a water-soluble carboxyvinyl polymer, and at least one of polyphosphate and / or phosphoric acid or a salt thereof.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Sucralfate used in the present invention is sucrose sulfate aluminum salt as described above. One example of the production method is to react sucrose polysulfate salt with aluminum ion and precipitate it by precipitation. There is a method in which the wet powder is separated and then dried by heating to obtain a dried product. Sucralfate is insoluble in water, and its particles are considered to be as fine as possible when applied to living organisms, considering the ability to adsorb to proteins, and it is important to increase the surface area. The product is preferably refined by a jet mill or the like.

The water-soluble carboxyvinyl polymer used in the present invention is a polymer of acrylic acid, for example, trade names, Carbopol (manufactured by BF Goodrich), Junron (manufactured by Nippon Junyaku), Hibiswacoal (manufactured by Wako Pure Chemical Industries, Ltd.) Medicine)
It is commercially available as

[0013] The peptizer used in the present invention includes:
Polyphosphates and / or phosphoric or phosphates are used. Examples of the polyphosphate include alkali metal salts such as sodium polyphosphate and potassium polyphosphate, and examples of the phosphate include sodium dihydrogen phosphate, disodium phosphate, potassium dihydrogen phosphate, and the like.
And dipotassium phosphate.

The suspension preparation of the present invention can be prepared by a conventional method.
(A) Sucralfate, (B) a water-soluble carboxyvinyl polymer, and (C) at least one compound selected from a polyphosphate and a phosphoric acid or phosphate.
Are preferably suspended in purified water. For the preparation method, for example, (1) a water-soluble carboxyvinyl polymer (B) is put into purified water with a sieve of about 20 mesh so as not to be clumped, and stirred and mixed until uniform. (2) Separately, sucralfate (A) and a sweetener or a flavoring agent, a thickener, and the like are added to purified water, and the mixture is stirred and mixed to make it uniform. Then, (3)
To the suspension obtained in (2), the liquid obtained in (1), a preservative, and the like are added, and after stirring, polyphosphate and phosphoric acid or phosphate (C) are added, and the mixture is uniformly mixed. Become.

In the present invention, the blending amount of sucralfate in the suspension is usually 0.1 to 50 w / v%, and the blending amount of the water-soluble carboxyvinyl polymer is 0.1.
２2 w / v%, the blending amount of polyphosphate, phosphoric acid or phosphate is 0.5-1 w / v%. Preferably, it is 0.1-20 w / v% of sucralfate, 0.2-1.5 w / v% of a water-soluble carboxyvinyl polymer, and 0.5-0.8 w / v% of a polyphosphate.

In the present invention, in addition to the above-mentioned components, a polyhydric alcohol such as glycerin or sorbitol is blended for the purpose of increasing the viscosity, or if necessary, a preservative or preservative, and Fragrances, sweeteners or flavoring agents.

The suspension formulation of the present invention is preferably stored in a plastic container at room temperature. If a single dose is provided as a preparation enclosed in a container made of polyethylene or polypropylene, sucralfate can be easily taken by simply opening the container at the time of administration. The amount of sucralfate to be administered at one time is usually about 0.5 to 2 g, so that the sucralfate of the suspension is adjusted to a volume of about 5 to 20 mL in consideration of ease of taking. Is preferably prepared.

[0018]

Next, the present invention will be described in detail with reference to examples. Example 1 A sucralfate suspension formulation having the following compounding ratio was prepared by the following method. Formulation Example 1 Sucralfate 10 g Carboxyvinyl polymer 2 g Saccharin sodium 0.02 g Sodium polyphosphate 0.8 g Propyl parahydroxybenzoate 0.05 g Fragrance Trace amount Purified water Appropriate amount 100 mL (Preparation method) (1) Carbovinyl polymer is added to 50 mL purified water And stirred until uniform. (2) Separately, sucralfate and saccharin sodium were added to 20 mL of purified water, and the mixture was stirred vigorously to make it uniform. (3) To the suspension obtained in (2), the liquid obtained in (1), propyl paraoxybenzoate, and a fragrance were added, and the mixture was stirred, and purified water was added to make a total volume of 100 mL. (4) Finally, sodium polyphosphate was added and uniformly mixed to obtain a total of 100 mL of sucralfate suspension. The following Formulation Examples 2 and 3 and Comparative Formulation Examples 1 and 2 were also prepared according to the above method.

Formulation Example 2 Sucralfate 10 g Carboxyvinyl polymer 1 g D-sorbitol solution 20 g Glycerin 6 g Sodium dihydrogen phosphate 0.4 g Sodium polyphosphate 0.7 g Propyl parahydroxybenzoate 0.05 g Perfume Trace amount 100 mL

Formulation Example 3 Sucralfate 10 g Carboxyvinyl polymer 0.3 g D-sorbitol solution 20 g Glycerin 8 g Sodium dihydrogen phosphate 0.4 g Sodium polyphosphate 0.7 g Propyl parahydroxybenzoate 0.05 g Perfume Trace amount 100 mL

Comparative Formulation Example 1 Sucralfate 10 g D-sorbitol solution 20 g Glycerin 8 g Sodium dihydrogen phosphate 0.4 g Sodium polyphosphate 0.7 g Propyl parahydroxybenzoate 0.05 g Perfume Trace amount 100 mL

Comparative Formulation Example 2 Sucralfate 10 g Carboxyvinyl polymer 0.3 g D-sorbitol solution 20 g Glycerin 8 g Propyl parahydroxybenzoate 0.05 g Fragrance Trace amount Total 100 mL

Test Example 1 Redispersibility test: Changes in redispersibility over time of the suspensions prepared in Formulation Examples 1 to 3 and Comparative Formulation Examples 1 and 2 were examined.
In this test, 10 mL of each sample was sealed in a polyethylene container, and immediately after production and at room temperature for 1 day and 1 day.
After standing for a week, the container was gently turned over and visually checked to see whether the particles were uniformly dispersed again. Table 1 shows the results.

[0024]

[Table 1]

Test Example 2 Sedimentation degree test: Changes in the sedimentation degree over time of the suspensions prepared in Formulation Examples 1 to 3 and Comparative Formulation Examples 1 and 2 were examined. In this test, 50 mL of each sample was sealed in a glass cylindrical tube, and the percentage of dispersion was measured immediately after production and after standing at room temperature for one day and one week. Table 2 shows the results.

[0026]

[Table 2]

As is apparent from Tables 1 and 2, the suspension preparation containing the carboxyvinyl polymer and sodium polyphosphate was easily re-equipped as compared with the preparation containing no carboxyvinyl polymer (Comparative Formulation Example 1). Could be dispersed. Further, compared to the preparation containing no sodium polyphosphate (Comparative Formulation Example 2), sedimentation was extremely difficult.

[0028]

As described above, the sucralfate suspension of the present invention is a white suspension that is difficult to settle, or even if settled, shakes the container at the time of use to uniformly redisperse sucralfate. It can be taken easily without being roughened in the oral cavity or adhering to mucous membranes when taken.

Claims (3)

[Claims] 1. A sucralfate suspension formulation containing sucralfate, a water-soluble carboxyvinyl polymer, and at least one of polyphosphate and / or phosphoric acid or a salt thereof. 2. The sucralfate suspension preparation according to claim 1, wherein the amount of the water-soluble carboxyvinyl polymer is 0.1 to 2 w / v% of the whole preparation. 3. The amount of at least one polyphosphate and / or phosphoric acid or a salt thereof is 0.1% of the total amount of the preparation.
The sucralfate suspension preparation according to claim 1 or 2, which is 5 to 1 w / v%.