JPS60174728A - Prolonged release pharmaceutical - Google Patents

Abstract

PURPOSE:An inexpensive prolonged release pharmaceutical, containing Plantago seeds containing a water-swellable mucilagions substance, and capable of forming a mucilaginous gel matrix and releasing a chemical component constantly at a givae ratio, and easily preparable. CONSTITUTION:A prolonged release pharmaceutical containing Plantago seeds of the genus Plantago of the family Plantaginacea. The amount of the Plantago seeds to be incorporated is 1-50%, preferably 10-30%. The Plantago seeds are well known as a purgative, but the action of forming mucilaginous gel matrix is novelly utilized to produce the aimed prolonged release pharmaceutical as a medicine. The gelation of the mucilaginous substance by hydration swells and expands the whole pharmaceutical and forms a matrix membrane. Thus, the release of the chemical component is controlled. The raw material Plantago seeds are more inexpensive than the raw material for the conventional brolonged release pharmaceutical without requiring special equipment nor step.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a long-acting preparation containing Plantago (Plantago seeds). Specifically, by incorporating plantago seeds that contain water-swellable mucilage. This invention relates to a sustained-release preparation that enables constant release of drug components gradually and at a constant rate.

One of the methods for producing long-acting pharmaceutical preparations is the film coating method. However, this method has problems with the occurrence of bottle holes and cracks due to coating conditions. There are problems with controlling sustained efficacy, such as high molecular weight drugs not being eluted. There are also economic problems such as the need for special manufacturing machinery or equipment, the need for large amounts of organic solvents during manufacturing, and pollution caused by the use of organic solvents. There are also explosion hazards and health problems for workers.

There is also a manufacturing method in which drugs are embedded in wax or hydrophobic polymeric substances. Due to the hydrophobic nature of such formulations, sufficient drug release is not possible. Bioavailability may be questionable. Furthermore, there are disadvantages such as the raw materials are expensive.

The present invention provides a new sustained-release formulation that eliminates the above-mentioned drawbacks. In other words, the gel-forming effect of polymers is thought to be effective in controlling drug release.

Based on this knowledge, we focused on natural polymeric polysaccharides.

The result of various considerations. This led to the present invention. The gist of this is a long-acting formulation containing Plantago seeds. The content of the seeds is preferably 1 to 50%. 10-30% is particularly preferred.

The sustained-release preparation according to the present invention is cheaper in raw materials than the raw materials for conventional specific-effect preparations, and does not require special equipment or processes during production.

In the sustained-release preparation according to the present invention. The gelation caused by the hydration of the mucilage contained in plankgo seeds causes the entire preparation to swell and expand, and a matrix film is formed, thereby making it possible to control the release of the aphrodisiac component.

The ingredients of the long-acting preparation in the present invention include those that are absorbed and excreted quickly and have a short blood half-life tZ, making it difficult to maintain efficacy, and conversely, those that are difficult to dissolve and absorb and therefore do not maintain effectiveness. Contains both ingredients that cannot be removed. In addition, known excipients, binders, disintegrants, etc. may also be included in order to further control the sustained effect.

Plantago seeds are listed in the Japanese Pharmacopoeia as well as the British Pharmacopoeia.
, The United St.
Pharmacopeia), Indian Pharmacopoeia (Th
e Indian Pharmaceutical C
odex), etc., and is used in medicine as a laxative.

Expect a laxative effect based on its expansion and lubricating action.

It is also used in diet foods, etc. Recently, there have been reports that plantago seeds have (1) an effect of lowering serum cholesterol levels in humans, (2) an effect of alleviating side effects of acetylsalicylic acid, and (3) an effect of preventing the accumulation of digoxin. However, these methods are based on the action of the mucilage of Plantago seeds on the stomach and intestinal mucosa, and are different from those that utilize the formation of a mucilage gel matrix as in the present invention.

Plantago 5eed is a species of the Plantago family, Plantago genus, such as Plantag.
o ovataForskal, Plantago
psylium Linn5, Plantag.

1ndica Linne, Plantago a
There are seeds such as Siatica Linnδ, and the epidermis contains mucilage. When mucilage is hydrated, it swells and becomes a viscous dispersion "gum."

The main component of mucilage is polysaccharides.
), and its constituent monosaccharide is L-Arabinose.
, D-Xylose.

L-Rhamnose, D-Ga1actose
etc. ! 1 gum" is 20-50℃ and pH 1-1
In the range of 0, its viscosity and swelling degree t hardly change and it is not digested and absorbed by the human body.

The mechanism by which Plantago seeds impart long-lasting effects to formulations is that they swell the mucilage, create a "gum" or gel matrix in advance, embed the drug therein, mold it, and then swell it again. One example is to form a gel matrix film on the outer layer of the drug to gradually elute the drug. The gel matrix of keratin maintains its shape to some extent even after swelling with hydration and is not digested and absorbed in the human body, making it more advantageous in controlling drug elution.

Japanese Pharmacopoeia disintegration test method 1st solution (pH
Table 1 shows the viscosity of 1 gel of Plantago seeds using Japan M fj4j disintegration test method second solution (pH about 6.8), which corresponds to approximately 1.2) and artificial intestinal fluid.

Type B rotational viscosity manufactured by Tokyo Keiki Seisakusho Rotor rotational speed 1 orpm Rotor A6 In addition, the swelling property of plantago seeds (SwellingPo
wer) is as shown in Table 2 in the above test solution.

Table 2: 1w/v% Examples are shown below and the present invention will be described in detail; however, the present invention can be widely used not only in the pharmaceutical field but also in the food field, and is not limited to the following examples.

Example 1 The components of formulations 1 to 7 shown in Table 3 are mixed uniformly and kneaded with water. Do this according to the usual method.

Granulate, dry, and crush into granules. Magnesium stearate in an amount equivalent to 1% by weight was added and mixed uniformly to produce tablets with a diameter of 5.5 mm and a weight of BOmg.

Next, the first liquid (artificial preliquid) was prepared according to the disintegration test method of the 10th Amendment 1-1 Honkuwa Pharmacopoeia, and the release status of chlorpheniramine maleate from each empty tablet of formulations 1 to 7 was measured. did.

In addition, regarding the chlorpheniramine maleate tablets (diameter approximately 5.5 mm, weight 80 mg per tablet) manufactured by the usual method without adding Plantago Obata seed Chigiwo, the chlorpheniramine maleate tablets were similarly extracted from the tablets. The release status was measured.

The results are summarized and shown in Figure 1.

As shown in the figure, the release of chlorpheniramine maleate from the tablets containing Plantago Obata Seed Chigi is delayed and continuous compared to the release from the tablets containing Plantago Obata Seed Chigi. This is clearly the first force, and also,
The effect increased as the amount of Plantago Obata Chigi added increased.

Example λ Table 4 Riboflavin 60g Plantago Obata seed powder 160g Lactose 500g Powdered sugar 400g Potato Denbun 500g The ingredients shown in Table 4 were the same as in Example 1.

The tablets had a diameter of 5.5ii and a weight of 80cm. Next, the release status of riboflavin from the tablets was measured in the same manner as in Example. In addition, the release status of boflavin from the tablets was similarly measured for boflavin tablets (approximately 5.5 mm in diameter, 80 μm in weight per tablet) that were manufactured by the usual method without adding blank Goobata seed Chigi. .

The results are summarized and shown in Figure 2.

As shown in the figure, similar to the results of Example 1, the combination of Plantago ovata seed Chigi had the effect of delaying and continuous release of riboflavin.

Example 3 Table 5 Riboflavin 60g Plantago Obata seed powder 480g Lactose 385g Powdered sugar 310g Potato starch 310g The ingredients shown in Table 5 are mixed uniformly and kneaded with water. This was granulated, dried, and crushed to obtain granules according to a conventional method. Next, the release status of boflavin from the granules was measured in the same manner as in Example 1. Furthermore, the release of boflavin from the granules was similarly measured for boflavin granules produced by a conventional method without incorporating Plantago Obata seed Chigi.

The results are summarized and shown in Figure 3.

As shown in the figure, as in Examples 1 and 2, it was possible to continuously release the drug over an extended period of time in the granules by incorporating Plantago Obata species Chigi.

Example q Chlorpheniramine maleate 60g - Plantago Obata Seed Chigi 1.680g Lactose 680g 1.40
0g Powdered sugar 400g 1.120g First, each component shown in Table 6 was mixed uniformly as an inner core tablet, and 10% hydroxypropyl cellulose solution (solvent;
0% ethanol). This is granulated, dried, and ground into granules according to a conventional method.

To this was added magnesium stearate in an amount equivalent to 1% by weight, and the mixture was mixed uniformly, using a pestle with a diameter of 5.5 mm to form an inner core tablet with a weight of 80 cm.

Next, for the outer layer part, the components shown in Table 6 are mixed uniformly and kneaded with a 10% hydroxypropylcellulose solution (water as the solvent). Do this according to the usual method.

Granulate, dry, and crush! 11li granules, add magnesium stearate equivalent to 1% by weight, and mix uniformly to form the outer layer.

Using the inner core tablet and outer layer part, one tablet weighs 360 mg (inner core i 80 mg
, outer layer; 280 rTlg) were produced.

Next, the release status of chlorpheniramine maleate from the dry-coated tablet was measured in the same manner as in Example 1.

The results were as shown in FIG.

As shown in the figure, by incorporating Plantago Obata Chigi into the outer layer, delayed and continuous release became possible.

[Brief explanation of drawings]

In the accompanying drawings, FIG. 1 is a graph showing the dissolution pattern of chlorpheniramine maleate in a tablet containing chlorpheniramine maleate according to the present invention. FIG. 2 is a graph showing the dissolution pattern of riboflavin in the riboflavin-containing tablet according to the present invention. FIG. 3 is a graph showing the elution pattern of riboflavin in the riboflavin-containing granules according to the present invention. FIG. 4 is a graph showing the elution pattern of chlorpheniramine maleate in the dry coated agent containing chlorpheniramine maleate according to the present invention. Patent Applicant Sato Pharmaceutical Co., Ltd. Representative Patent Attorney 1) H Tomari Figure 1 Figure 2

Claims (1)

[Claims] (1) Plantago 5eed
). -) The formulation according to claim (1), wherein the blended amount of plantago seeds is 1 to 50%.