Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1995-06-15
1997-06-10
Dodson, Shelley A.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424495, A61K 920, A61K 922
Patent
active
056373228
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for producing a composition for solid medicine, comprising, as an active ingredient, a potassium channel activator (potassium channel opener) useful as an antihypertensive agent and so on. More particularly, the present invention facilitates the control of elution of a potassium channel activator, by formulating same into solid preparations by dissolving a potassium channel activator in a solvent to give a medical solution, homogeneously mixing said solution with a water-insoluble cellulose or cellulose derivatives and removing the solvent by drying.
2. Description of Related Art
A potassium channel activator is an active substance which acts on a potassium channel of cell membranes, and is expected to be effective as an antihypertensive drug and a therapeutic drug for angina pectoris. Typical compounds having such activity are pyridine derivatives such as nicorandil and pinacidil, and chromane derivatives represented by chromakalim, and chromane derivatives have been particularly intensively studied.
The above-mentioned potassium preparations generally show high effects as an antihypertensive agent or coronary vasodilating agent in an extremely small dose. Hence, too rapid a dissolution thereof results in problematic side-effects such as sudden hypotension. Too slow a dissolution thereof, however, makes it difficult to attain sufficient efficacy. In other words, control and adjustment of elution rate are extremely critical for the drug of this kind.
Incidentally, potassium channel activators such as the above-mentioned chromane derivatives and pyridine derivatives are mostly solid chemical substances. When using such solid chemical substance as an active ingredient, said compound is generally produced with great care. However, the compound is not free from variation in the shape and particle size of crystals, and every lot tends to have a different elution rate. A method for controlling the elution rate of these solid drugs has been, for example, a method comprising pulverizing drug crystals to afford uniform particle size of the crystals or a method comprising controlling the elution rate by coating the drug with a mixture of water-soluble and water-insoluble polymers. Yet, pulverizing crystals in a certain range with good reproducibility is not easy, and control of elution rate relying on pulverizing is associated with difficulty. The method comprising coating of the drug is also defective in that the production steps become complicated and the cost tends to be higher.
The excipients for solid preparations such as powder, granule and tablet include, for example, organic excipients such as saccharides (e.g. lactose, glucose, mannit and sorbit), starches (e.g. corn starch and dextrin), celluloses [e.g. crystalline cellulose (MCC), low substituted hydroxypropyl cellulose (L-HPC) and internally crosslinked sodium carboxymethyl cellulose (CMC-Na)], gum arabic, dextran and pullulan; and inorganic excipients such as light anhydrous silicate, synthetic aluminum silicate, calcium phosphate, sodium carbonate and calcium sulfate. Of these, crystalline cellulose permits direct compression and is applied to a wide range of use such as capsule filling auxiliary, granulating auxiliary for granules and spherical granules, oil-absorber and the like, besides the use for compression. As a preparation method using cellulose, the technique such as the following is known.
That is, Japanese Patent Unexamined Publication No. 38322/1985 describes a method for obtaining easily-soluble solid preparation, comprising dissolving a dihydropyridine A, which is useful as an antihypertensive agent or coronary vasodilating agent, in an organic solvent such as chloroform, adding hydroxypropylmethyl cellulose, which is a water-soluble polymer, to this solution to give a homogeneous solution, and removing the organic solvent. The easy dissolution of the drug is ensured by the use of a water-soluble cellulose derivative, unlike control of elution
REFERENCES:
patent: 4656027 (1987-04-01), Sjoovist
patent: 4720387 (1988-01-01), Sakamoto et al.
patent: 4822808 (1989-04-01), Lida et al.
patent: 5011837 (1991-04-01), Atwal et al.
patent: 5250547 (1993-10-01), Lochead et al.
patent: 5447943 (1995-09-01), Lochead et al.
Ogawa Kenji
Sugimori Ken-ichi
Tamura Kiyoshi
Dodson Shelley A.
Japan Tobacco Inc.
Yoshitomi Pharmaceutical Industries Ltd.
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