1. Field of the Invention
The present invention relates to an inclusion compound composed of tripamide and cyclodextrin.
2. Brief Description of the Prior Art
Tripamide which is to be included in accordance with the present invention is named N-(4-A2a-endo-tricyclo[5.2.1.0.sup.2.6. ]decan-4-yl)-4-chloro-3-sulfamoylbenzamide shown by structural formula: ##STR1## and commercially available as a curing agent of essential hypertension. However, this substance is soluble in water only with extreme difficulty. In actuality, it is understood that the solubility of the substance in water, the solubility in the Liquid I used for the disintegration test of the Japanese Pharmacopoeia (hereinafter referred to "Liquid I of the Japanese Pharmacopoeia") and the solubility in the Liquid II used for the disintegration test of the Japanese Pharmacopoeia (hereinafter referred to "Liquid II of the Japanese Pharmacopoeia") is low, as is seen from the sample for comparison in Example 2 later described. Liquid I of the Japanese Pharmacopoeia is prepared by adding, to 2.0 g of sodium chloride, 6.0 ml of a diluted hydrochloric acid and water, so as to make the total volume to 1000 ml. The Liquid I is colorless and transparent, and its pH is about 1.2. Liquid II of the Japanese Pharmacopoeia is prepared by adding, to 35.8 g of sodium monohydrogenphosphate, 6.0 ml of a diluted hydrochloric acid and water, thereby making the total volume to 1000 ml. The Liquid II is colorless and transparent, and its pH is about 7.5.
Techniques for improving solubility of pharmaceuticals using cyclodextrin are already widely known in the art. For example, upon improvement of the solubility of pharmaceutical compounds such as barbituric acid derivatives, mefenamic acid, indomethacine, chloramphenicol, etc., it is known that cyclodextrin exhibits its best usefulness. However, the usefulness is not obviously applicable to general pharmaceuticals, but has been developed only by discovering respective applications corresponding to respective pharmaceuticals. In attempting to apply to tripamide, techniques specific to tripamide have been taken into account and by confirming the formation of an inclusion compound and the improved solubility thereby, the present invention has been perfected.
Under the foregoing circumstances, the present inventors have extensively investigated methods of improving the solubility of tripamide and as a result, have found that the aimed object has been achieved by converting the substance into an inclusion compound using cyclodextrin as a host and, have accomplished the present invention.
USPTO Backgrounds
USPTO Backgrounds