Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Patent
1999-03-31
2000-10-31
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
424433, 424434, 424451, 424422, A61F 902
Patent
active
061398632
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a rectal suppository comprising the active ingredient, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) benzimidazole in the following formula (I), which exert drug having serotonin.sub.3 antagonistic activity. ##STR2##
BACKGROUND ART
A rectal suppository has the following benefits: the possibility of dosing with a relatively larger amount of drug than that by the oral or injection route, avoiding of disorders of digestion, safety in comparison with injection, avoiding of the decomposition and metabolism in comparison with oral administration, absence of an effect on feeding, expectation of continuous treatment before and during sleep, the possibility of dosing to children and elderly patients who have difficulty in swallowing or who have difficulty in receiving injection, absence of the necessity for a doctor or nurse for administration such as received for injection and the suitability for home therapy. Based on the features descrived above, many rectal suppositories have recently been used for systemic and local therapy in clinical and home treatment.
It has been shown that 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) benzimidazole (I) (hereinafter referred to briefly as benzimidazole derivative (I)) which has serotonin.sub.3 antagonistic activity, is effective in inhibiting vomiting caused by the administration of chemotherapy such as cisplatin (Japanese Patent Unexamined Publication No. 17449/1993). Furthermore, benzimidazole derivative (I) is already known to be an effective ingredient as a remedy for irritable bowel syndrome based on serotonin.sub.3 antagonistic activity (Japanese Patent Unexamined Publication No. 145152/1994).
In the Patent Publications cited above, it has been described that said compound has been formulated into injectable and oral dosage forms such as tablets, granules, etc.
However, said oral dosage form is unsuitable because of the difficulty in administering to patients who have difficulty in swallowing due to vomiting, etc. Futhermore said injection is unsuitable because of pain caused by the multiple administration, and is also inappropriate for home therapy.
In Japanese Patent Unexamined Publication No.48258/1995, percutaneous dosage forms such as the patch and ointment comprising the benzimidazole derivative (I) as the active ingredient having serotonin.sub.3 antagonistic activity have been disclosed. However, the suppository comprising the benzimidazole derivative (I) as the active ingredient is unknown.
DISCLOSURE OF THE INVENTION
The object of the invention is to provide a novel rectal suppository comprising a benzimidazole derivative (I) in the following formulation, which assures efficient absorption and good storage stability of the benzimidazole derivative (I) in the following formulation. The finding which has culminated in the present invention is that a benzimidazole derivative (I) is well absorbed by rectal adminstration, and that an oleaginous base, generally a hard fat with a hydroxy value not exceeding 50, preferably with a hydroxy value not exceeding 15 have shown excellent storage stability of the benzimidazole derivative (I). Furthermore, the inventor of the present invention performed assiduous research to improve the rectal absorption and storage stability of benzimidazole derivative (I), adding a cysteine hydrochloride or hydrate thereof to the suppository .
EXPLANATION OF FIGURE
FIG. 1 shows the mean plasma concentration profiles of benzimidazole derivative (I) after the rectal administration of the suppository A (.largecircle.), B (.quadrature.) and C (.circle-solid.), which are prepared for rats, corresponding to Example 1, 4 and 6 respectively.
BEST MODE FOR EXECUTION OF INVENTION
Benzimidazole derivative (I) used in the present invention is synthesized by the method previously described in Japanese Patent Unexamined Publication No.17449/1993.
The rectal suppository according to the present invention may be manufactured to dissolve or suspend benzimidazole derivative (I
REFERENCES:
patent: 5246704 (1993-09-01), Sakaguchi
patent: 5407936 (1995-04-01), Suzuki et al.
patent: 5635520 (1997-06-01), Uda
patent: 5661142 (1997-08-01), Naeger
Ghali Isis
Kanebo Ltd.
Page Thurman K.
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