JP3496158B2 - Gelatin capsule preparation containing tranexamic acid - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cold remedy, an antipyretic analgesic or an antitussive / expectorant drug, which has improved efficacy and improved the time delay from administration to the onset of efficacy.

[0002]

2. Description of the Related Art Cold remedies, antipyretic analgesics, and antitussives and expectorants are used for various symptoms related to chill fever, headache, cough, sore throat, nasal congestion, etc., depending on the purpose of each drug. Various corresponding medicinal properties are blended. However, in relieving symptoms such as a cough and a sore throat caused by a cold or bronchitis, it is difficult to say that they have always exerted a sufficient effect.

[0003] In general, cold remedies, antipyretic analgesics, and antitussive and expectorant drugs, tablets or powder-filled hard capsules are commonly used. However, these cold medicines and other drugs often contain poorly soluble ingredients as the medicinal ingredients, and tablets and hard capsules are difficult to absorb these poorly soluble medicinal ingredients after administration. There was a considerable time delay.

[0004]

In view of the above problems of conventional cold medicines, antipyretic analgesics and antitussive and expectorant preparations, the present invention increases the effects of these medicines on cough and sore throat and at the same time from administration. It is an object of the present invention to provide a more excellent drug that can significantly reduce the time delay until the onset of drug effect.

[0005]

[Means for Solving the Problems] As a result of examination, in order to enhance the efficacy of conventional cold medicines for coughing, sore throat, etc.,
It has been found to be effective to further add tranexamic acid, which has an anti-inflammatory effect, in addition to the conventional ingredients.
That is, tranexamic acid is known to suppress the enhancement of vascular permeability as well as the production of the causative substance of inflammatory lesions, and is considered to be effective in relieving the inflammatory symptoms associated with the common cold. Therefore, by adding tranexamic acid in addition to the components of the conventional cold medicine and the like, the effects of these conventional medicines can be enhanced.

On the other hand, in order to shorten the time delay from administration to the onset of drug effect, it is necessary to rapidly dissolve each active ingredient after administration. Instead of conventional tablets or hard capsules, It has been found that it is extremely effective to prepare a formulation in which each medicinal component is suspended in a liquid carrier and contained in a gelatin capsule. Furthermore, it was also confirmed that such suspension of each active ingredient in a liquid medium kept the stability of each active ingredient high and could withstand use as an actual formulation. In the present specification, "suspension" includes not only suspension in a strict technical sense but also widely dispersed state, and emulsified state as well as partially dissolved state.

That is, the present invention is a cold remedy, an antipyretic analgesic or an antitussive expectorant, which contains tranexamic acid as one of the medicinal components, and the medicinal components are suspended in a liquid carrier and included in a gelatin capsule. It is a gelatin capsule preparation characterized in that

The blending amount and blending ratio of tranexamic acid is
The content varies depending on the amount of the other active ingredient compounded, the volume of the gelatin capsule, and the amount of the liquid carrier used, but cannot be uniformly determined. However, the content ratio of the gelatin capsule is, for example, 0. In the case of 25 g, it can be 5 to 30% by weight of the content, and usually, for example, 10 to 20% by weight is preferable.

As an active ingredient other than tranexamic acid,
The active ingredients used in conventional cold remedies, antipyretic analgesics or antitussives and expectorants can be appropriately used. As an antipyretic analgesic,
For example, lactylphenetidine and acetaminophen are preferable, as the antitussive expectorant, for example, dl-methylephedrine hydrochloride is preferable, and as the common cold drug, in addition to these, for example, as an antihistamine, d- or dl-chlorpheniramine maleate, Although isothipendyl hydrochloride is preferred, it is not limited thereto, and any other active ingredient usually contained in these drugs can be used.

As the liquid carrier for suspending the active ingredient, a mixture of medium-chain fatty acid triglyceride, edible oils and fats such as corn oil and safflower oil, and a thickening agent such as beeswax is suitable, and necessary. According to the above, an emulsifier such as polysorbate 80 may be further added. The liquid carrier can be appropriately used in such an amount that the active ingredient is uniformly suspended with respect to the total amount of the active ingredient so that the whole becomes liquid. For example, it is usually preferable to add about 2 parts by weight to 1 part by weight of the active ingredient, but 1 part by weight to 4 parts by weight can be used for 1 part by weight of the active ingredient.

The viscosity of the liquid can be adjusted by the amount of thickener and emulsifier. For example, thickeners are usually added to make up 1 to 8% of the liquid carrier, and emulsifiers are usually added to make up 0 to 10% of the liquid carrier. . However, the liquid carrier is not limited to these ranges, and can be appropriately adjusted to obtain the desired viscosity of the liquid carrier.

The suspension of the active ingredient in the liquid carrier is carried out by dissolving the vegetable oil, the thickener and, if necessary, the emulsifier while heating.
This can be achieved by mixing and, after reaching a suitable temperature, small amounts of the respective medicinal components as a cold medicine, antipyretic analgesic or antitussive expectorant, and mixing until uniform. The suspension is then filled into a gelatin capsule by a conventional method and included therein to obtain the preparation of the present invention.

[0013]

【Example】

Method for Producing Gelatin Capsule Formulation of the Present Invention Gelatin capsules including a suspension comprising the following components were all well produced. Each of the prescriptions is as a cold medicine, and the prescription amount is the daily dose for adults. The manufacturing method is as described above.

[0014]

[0015]

[0016]

[0017]

[0018]

[Test Example 1] Stability test of each liquefied active ingredient The storage stability of the gelatin capsule preparation of the present invention was measured. (1) Sample: Gelatin capsules (content 0.25 g) produced according to Example 1 were used. (2) Test method: Storage condition 1: 40 ± 1 ° C., relative humidity 75 ± 5% Storage condition 2: Room temperature test period: 6 months Measurement period: At the time of test disclosure and after 1, 3 and 6 months Measurement method: High-speed liquid Chromatography (3) results: Changes in the quantitative value of each component are shown in FIGS. As shown in these figures, each active ingredient showed excellent stability in the preparation of the present invention.

Test Example 2 Dissolution of Active Ingredient The gelatin capsule preparation of the present invention was evaluated for dissolution by the dissolution test. (1) Test sample: Gelatin capsules (content: 0.25 g) manufactured according to Example 1 were used. (2) Control sample A: Amount corresponding to Example 1 (35 m
g) Tranexamic acid in a total amount of 0.25 with powdered excipient
Hard capsule formulation filled as g. Control Sample B: A tablet made of tranexamic acid in an amount corresponding to Example 1 (35 mg) with a powder excipient to a total amount of 0.25 g. (3) Test method: Among the dissolution test methods of the Japanese Pharmacopoeia General Test Method, the paddle method was used for the test. The eluate was collected for 3 hours after the start of the test, and tranexamic acid and lactylphenetidine were quantified by high performance liquid chromatography to measure the elution amount. (4) Results: Despite being suspended in an oily liquid carrier, both tranexamic acid and the sparingly soluble lactylphenetidine in the test sample showed extremely good dissolution patterns (Fig. 5 and (Figure 6). Further, as is clear from FIG. 6, the elution of tranexamic acid from the preparation of the present invention was
Hard capsule formulation (control sample A) and tablet (control sample B)
It was much faster than the elution of tranexamic acid from any of the above.

[Brief description of drawings]

1 is a graph showing the stability of lactylphenetidine in the formulation of Example 1. FIG.

FIG. 2 is a graph showing the stability of dl-methylephedrine hydrochloride in the preparation of Example 1.

FIG. 3 is a graph showing the stability of d-chlorpheniramine maleate in the preparation of Example 1.

FIG. 4 is a graph showing the stability of tranexamic acid in the preparation of Example 1.

FIG. 5 is a graph showing the elution properties of lactylphenetidine from the preparation of the present invention.

FIG. 6 is a graph showing the dissolution properties of tranexamic acid in the conventional preparation and the preparation of the present invention.

Continuation of the front page (56) Reference JP-A-62-249922 (JP, A) Noriaki Nakatani, Use of the cold drug K-CW with tranexamic acid for cold syndrome, 1990, vol. 18, No. 2, 799-808 (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K 31/00-31/80 A61K 9/48 A61P 11/00-11/16 A61P 29/02 CAPLUS (STN) JISST File (JOIS) MEDLINE (STN)

Claims (2)

(57) [Claims] 1. A cold medicine comprising at least an antipyretic analgesic, an antitussive, an antihistamine and tranexamic acid, wherein these active ingredients are suspended in an oily liquid carrier and encapsulated in a gelatin capsule. Soft capsule cold drug formulation. 2. A formulation according to claim 1, wherein the oily liquid carrier comprises an edible oil and / or a medium chain fatty acid triglyceride, a thickener and optionally an emulsifier.