JP3285198B2 - Liquid for internal use - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid medicine for internal use, and is used in the medical field.

[0002]

2. Description of the Related Art Conventionally, tablets and capsules have been widely used as preparations for internal use, but these preparations are particularly aging due to their shape and size. In some cases, it is difficult for the elderly to take the drug, and in recent years, with the increase in the elderly, there has been a demand for an oral preparation that can be easily taken by the elderly.

[0003] Liquid medicines for internal use are easy to take even for elderly people because the components are dissolved and are in a liquid state, and meet such needs. However, when a liquid medicine for internal use is newly developed, Bioequivalence with tablets and capsules already on the market is required. In general, in liquids, the active ingredient is already in a dissolved state, and when administered to a living body, the active ingredient is released from the preparation and released into the gastrointestinal tract, compared to tablets and capsules, which require a longer time for the active ingredient to dissolve. The rate of mixing with the liquid is fast. Therefore, the problem is how to control the release rate of the main drug component from the liquid drug and make it the same as the dissolution rate of tablets and capsules, and ensure the bioequivalence of the two when administered to the living body. was there.

[0004]

Means for Solving the Problems The inventors of the present invention provide:
Surprisingly, by adding a sugar alcohol to a liquid medicine for internal use and adjusting the amount of the sugar alcohol added, the release rate of the main drug component from the liquid medicine can be changed and the mixing with the liquid in the digestive tract can be freely controlled. Was found.

[0005] Then, the sugar alcohol is added to the solution in an amount of 3 to 8 W.
It has also been found that the addition of / V% results in a release rate of the main drug equivalent to that of ordinary tablets and capsules, and a liquid preparation for internal use that can ensure bioequivalence with these preparations.

[0006] In the present invention , the release of the main drug component from the liquid preparation can be delayed by adjusting the addition amount of the sugar alcohol in the liquid preparation to be taken and increasing the addition amount of the sugar alcohol. By reducing the amount of the compound added, the release of the active ingredient from the liquid preparation can be accelerated. In this specification, "release of the main drug component from the liquid for internal use" means that the main drug component in the liquid for internal use is released and mixed with the liquid in the digestive tract.

[0007] Oite this inventions, as the principal agent ingredient that can control the release state, and are not be administered orally, H 2 receptor blocking anti-secretory agents, e.g., cimetidine, famotidine, nizatidine, and the like ranitidine hydrochloride.

[0008] Examples of sugar alcohols added for controlling the release rate of the main drug component include sorbitol, mannitol, xylitol, erythritol, maltitol and the like, with sorbitol being preferred.

[0009] The amount of sugar alcohol may be appropriately determined in accordance with the rate of release of the agent components from the desired solution, when the amount of its 3 ~8W / V%, usually tablets or capsules A liquid agent equivalent to the release (elution) rate of the main drug component from is obtained. In addition, when it is desired to delay the release of the main drug component from the liquid preparation and maintain the efficacy of the drug, more than 15 W / V% of the sugar alcohol is added to the upper limit of the solubility (for example, sorbitol) according to the release rate. Then, the required amount may be added up to 90 W / V%).

[0010] The oral solutions of this invention, H2 receptor
It contains a blocking antisecretory agent and 3-8 W / V% sugar alcohol.

[0011] The agent component used in the oral solutions of the present invention, although the above-described H 2 receptor blocking antisecretory agents, more preferably sheet Mechijin. The content of the main drug component in the liquid for oral administration varies depending on the type of the prescription drug, but is usually 0.1 to 20 W / V%, preferably
0.5 to 10 W / V%.

On the other hand, the sugar alcohol used is the same as described above, but sorbitol is preferred. When the added amount of the sugar alcohol is 3 to 8 W / V%, a liquid preparation having a release rate equivalent to the dissolution rate of the main drug component from ordinary tablets and capsules can be obtained.

The liquid preparation for internal use according to the present invention contains, in addition to the above sugar alcohol, a flavoring agent (for example, sucrose, glucose, fructose,
Maltose, lactose, saccharin sodium, dipotassium glycyrrhizinate, etc.), sour agents (eg, citric acid, tartaric acid, malic acid, etc.), coloring agents (eg, yellow No. 5, caramel, etc.), preservatives (eg, parabens), Additives used in normal liquids, such as thickeners (eg, methylcellulose), solubilizers (eg, hydrochloric acid), fragrances (eg, natural or synthetic flavors), and stabilizers may be added as appropriate. .

The liquid preparation for internal use of the present invention can be produced by a conventional method. One example is to dissolve the main drug component in purified water using a suitable solubilizing agent, and then add the sugar alcohol or other It is manufactured by adding an additive, stirring and dissolving.

[0015]

(1) Dissolution test (test sample) Cimetidine solution (Example 1 , Reference Examples 1, 2 and Production Example 1 described below) Cimetidine tablet: 200 mg tablet of Tagamet (manufactured by Fujisawa Pharmaceutical Co., Ltd.) (Test method) In a beaker of the dissolution test method of the Japanese Pharmacopoeia, 900 ml of the dissolution test solution (1st solution of the Japanese Pharmacopoeia) and glass beads 7 mm in diameter were added.
00g and kept at 37 ° C. The paddle with the teflon baffle was rotated at 13 rpm to allow the glass beads to move slowly with the baffle. When the test sample is put into the beaker, one tablet is put directly into the beaker, and the liquid is 10 ml (cimetidine 200 m
g) was collected with a whole pipette and injected into the bottom of a beaker. Sampling was performed at about 5 mm from the liquid level using a syringe, and the concentration of cimetidine was measured by HPLC. (Test results)

[Table 1]

(2) Oral Absorbency Comparison Test (Test Method) To nine male beagle dogs fasted overnight, 10 ml of the liquid preparation of the present invention (Example 1) and one cimetidine tablet used in the above (1) were added to Orally with 30 ml of water each,
After collecting blood at 10, 20, 30 minutes, 1, 1.5, 2, 4, 6 and 8 hours after administration, the concentration of cimetidine in blood was measured by HPLC,
AUC (0-8 hours), Cmax and Tmax were determined. (Test results)

[Table 2]

From the results in Table 1, in the present invention,
By increasing the sorbitol content, the release of cimetidine from the liquid preparation can be slowed, and by setting the sorbitol content to 5 W / V %, a release rate equivalent to that of a tablet can be exhibited. Also, from the results in [Table 2], the liquid preparation of the present invention shows oral absorbability equivalent to that of tablets.

[0018]

Example 1 Cimetidine (2.0 g) and a small amount of special grade hydrochloric acid were added to purified water (80 ml) to dissolve cimetidine, and then D-
Sorbitol (5 g), saccharin sodium (1.6
g), dipotassium glycyrrhizinate (0.1 g) and methyl paraben (0.1 g) were added, and the mixture was stirred, and the total amount was made up to 100 ml with purified water to obtain a liquid preparation.

Reference Example 1 The procedure of Example 1 was repeated except that the amount of D-sorbitol was 10 g, to obtain 100 ml of a liquid preparation.

Reference Example 2 The procedure of Example 1 was repeated, except that the amount of D-sorbitol was 15 g, to obtain 100 ml of a liquid preparation.

Production Example 1 100 ml of a liquid preparation was obtained in the same manner as in Example 1 without adding D-sorbitol.

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Norio Ohnishi 10 Kita Zojiro-cho, Saga Tenryuji, Ukyo-ku, Kyoto-shi, Kyoto (56) References JP-A-1-242524 (JP, A) Table 6-501003 (JP, A) European Patent Application Publication 836553 (EP, A1) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 9/08 A61K 47/10

Claims (2)

(57) [Claims] 1. A liquid preparation for internal use containing cimetidine and 3-8 W / V% sugar alcohol. 2. The liquid preparation for internal use according to claim 1, wherein the sugar alcohol is sorbitol.