JPS5967223A - Prolonged release type cefadroxil pharmaceutical - Google Patents

Abstract

PURPOSE:A prolonged release type cefadroxil pharmaceutical, prepared by incorporating a cefadroxil pharmaceutical disintegrable in the stomach with an enteric cefadroxil pharmaceutical, having prolonged action on blood concentration without delay in the initial concentration by the oral administration, and useful as an antimicrobial agent. CONSTITUTION:A prolonged release type pharmaceutical prepared by incorporating (A) a cefadroxil pharmaceutical disintegrable in the stomach with (B) an enteric cefadroxil pharmaceutical. The mixing potency ratio is preferably (30- 50):(70-50). The cefadroxil pharmaceutical disintegrable in the stomach (A) is preferably fine particles or granules disintegrable in the stomach, and the enteric cefadroxil pharmaceutical (B) is perferably fine particles or granules obtained by coating the pharmaceutical disintegralbe in the stomach (A) with an enteric film substance, e.g. ''Eudragit'' or carboxymethyl ethyl cellulose. The resultant pharmaceutical maintains the blood concentration at the time of administration for a long time without delay in the initial concentration.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a long-acting cefadroxil preparation. Cefadroxil is well absorbed from the gastrointestinal tract when administered orally, so it is a useful drug that is widely used as an oral drug for many infectious diseases. It is an antibacterial substance.

When cefadroxil is administered orally, it is difficult and rare to maintain the therapeutically necessary blood concentration for a long period of time due to rapid grass clearance.

The present inventors have conducted extensive studies on methods for rapidly developing and sustaining the blood concentration of cefadroxil when administered orally, and have found that gastric-soluble formulations of cefadroxil and enteric-coated formulations of cefadroxil. It has been discovered that when the preparation of the present invention, which is prepared by mixing with the preparation, is orally administered, there is no delay in the initial concentration and a sustained blood concentration is shown.
The invention has been completed.

That is, an object of the present invention is to provide a useful cefadroxil preparation that can be maintained for a long period of time without causing any delay from gastric-soluble preparations of cefadroxil and enteric-coated preparations of cefadroxil.

The gastric soluble preparation of cefatrexil used in the present invention contains cefatrexil and lactose.

Excipients and binders such as white sugar, cyclodextrin, starch, gum avia, and microcrystalline cellulose.

By adding a disintegrant or the like as appropriate, the preparation can be obtained using a known formulation method, and may be in the form of a powder, but preferably in the form of fine particles or granules.

In addition, enteric-coated preparations of cefadroxil include fine particles and granules made by coating the above-mentioned gastric-soluble preparations with enteric coating substances. Examples of enteric coating substances include Eudragit, cellulose acetate phthalate, carboxymethyl ethyl cellulose, etc. In the enteric-coated method, the mixing ratio of gastric-soluble preparation and enteric-coated preparation of cefadroxil is generally 20 to 60 to 80 to 40 in potency ratio, but preferably 30 to 40.
-50 to 70-50.

The present invention will be explained in more detail below using examples of granule production.

Example 1 (1) Se7 Adroxyl 6709. Lactose 222Q
,) Mix 689f of cornstarch starch, add 340g of corn starch paste () Add 300ml of water to 40g of cornstarch starch and heat and stir.) After kneading, granulate with an extrusion granulator, Dry under reduced pressure for 4 hours at °C. The obtained dried product was sized using a Huitumil, and the particle size was 20.
710 g of gastrosoluble granules of ~35 meh were obtained.

Next, 710 g of the gastric soluble granules were placed in a coating pan and spray coated using an alcoholic solution of Eudragit L in a conventional manner to obtain 880 g of enteric granules of Cefadroxil.

(2) Gastrosoluble granules prepared separately in the same manner as in (1) and f
The titer of enteric coated granules of l+ was measured, and both granules were mixed so that the titer ratio was 3:7 to form a mixed granule 1170.
I got a 9.

The blood concentration of the mixed granules obtained in Example 1 above and the gastric soluble and i-soluble granules as a control were measured upon oral administration using rabbits.

The dose was 25°C titer/#rabbit, and the sample was filled into a capsule and administered. Measurement of blood concentration is performed using 5arcina
The test was carried out using the 1utea AT CC9541 strain by the cylindrical plate method.

Figure 1 shows the time course of the blood concentration. The results show that the mixed cefadroxil granules of Example 1 maintain a high blood concentration for a longer time than the comparative gastric and enteric soluble granules.

Example 2 (1) Cefadroxil 110g, refined white sugar 54g
9L saccharin sodium 1g and gum arabic powder 4
09 are mixed, and 120 g of water-containing acetone is added and kneaded. After granulating this kneaded product with an extrusion type granulator,
Dry under reduced pressure for an hour. The obtained dried product was sized using a Futumil to obtain 730 g of gastric soluble granules having a particle size of 20 to 55 meah.

Next, 760 g of the above gastric soluble granules were placed in a coating pan, and spray coating was performed using an alcoholic solution of Eudragitsu F'L in a conventional manner to obtain 940 g of enteric granules of Cefadroxil.

(2) Gastric soluble granules prepared separately in the same manner as in (1) and 0
) of enteric-coated granules, and the titer ratio of these was 3.
Mixed granules 118 (:
I got 49. This was packaged in aluminum foil in a conventional manner, with a fi of 1.4 g per pocket (100'' being the titer).

Example 3 (1) Cefadroxil 2795g, lactose g40
Mix 15g of L silicic anhydride and add 12g of cornstarch paste liquid.
50! Add and knead. This kneaded product is granulated using a 1-box 1-out granulator, and then dried under reduced pressure at 50° C. for 4 hours.

The obtained dried product was sized using a Huitumil, and the particle size was 20 to 35.
Gastric soluble mesh granules 2510p were obtained.

Next, 2510 g of the above gastric soluble granules were placed in a coated bag, and sys-spray coating was performed using an alcohol bath solution of carboxymethylethyl cellulose in a conventional manner.
3050 g of enteric-coated granules of cefadroxil were obtained.

7- II Gastric soluble granules prepared separately in the same manner as il+ and +
After measuring the potency of P & soluble granules No. 11 and mixing both granules so that the titer ratio was 3, 30 g of magnesium stearate was further mixed to obtain mixed granules No. 41.
5Ωy was obtained. This was filled into six gelatin capsules in a conventional manner, each capsule containing 1fi360.

[Brief explanation of the drawing]

FIG. 1 is a formulation of the present invention of cefadroxil. When gastric-soluble granules and enteric-coated granules are orally administered, Bonagraph shows the changes over time in the blood distribution of cefatroxil for each preparation. -day -

Claims (1)

[Scope of Claims] (1) A long-acting cefadroxil preparation comprising a solution-soluble cefadroxil preparation and an enteric-coated cefadroxil preparation. (2) The enteric-coated cefadroxil preparation is a gastric-soluble powder, fine granules, or granules of cefadroxil. 2. The long-acting cefadroxil preparation according to claim 1, which is a fine granule or granule prepared by applying an enteric coating to the cefadroxil preparation. The long-acting cefadroxil preparation according to claim 1, wherein the enteric-coated cefadroxil preparation and the enteric-coated cefadroxil preparation are comprised in a ratio of 20 to 60 to 80 to 400 titers. . (5) The gastric soluble fine particles or granules of cefadroxil and the haliform fine particles or granules of cefadroxil contain 20
5. The long-acting cefadroxil preparation according to claims 1 and 4, comprising a potency ratio of ~60:80-40.