Claims
- 1. A method of treating a patient with a bacterial infection, comprising orally administering an antibacterial effective amount of 3-(N-piperidinomethylazino)methylrifamycin S to said patient.
BACKGROUND OF THE INVENTION
This is a continuation-in-part of U.S. patent application Ser. No. 07/304,033 filed Jan. 31, 1989.
The present invention relates to a pharmaceutical composition comprising 3-(N-piperidinomethylazino)methylrifamycin S as the active ingredient.
U.S. Pat. No. 4,447,432 and the corresponding U.K. Pat. No. 2,110,677 and Japanese LOP 92682/83 (application No. 199147/82), all in the name of the present applicants, disclose and claim azino-rifamycin compounds of formula ##STR1## as well as the corresponding oxidized quinones.
Such compounds are provided with strong antibacterial activity against Gram-positive and Gram-negative bacteria and especially against Mycobacterium tuberculosis.
It is known that rifampicin is the basic rifamycin derivative worldwide used against Mycobacterium Tuberculosis.
Many other rifamycin derivatives have been discovered and patented in the past years.
The most promising of the known rifamycin derivatives, including rifampicin, have been studied and compared with each other by Jean M. Dickinson and D.A. Mitchison of the Department of Bacteriology, Royal Postgraduate Medical School of London who have concluded that the 3-(N-piperidinomethylazino)methylrifamycin SV (labelled by the patentees as "FCE 22250") has the most important bactericidal activity and it is the most effective sterilizing drug having also a long half-life. Such results have been published on TUBERCLE (1987) 68, 183-193.
The outstanding biological characteristics including anti-bacterial activity and favourable pharmacokinetic properties of FCE 22250 on laboratory animals are reported in THE JOURNAL OF ANTIBIOTICS, Vol. 38, No. 6, pp. 779-786, June 1985: the laboratory animals were treated by oral route but especially intravenously with the cited drug.
Further accurate tests carried out "in vivo" by oral administration of FCE 22250 have shown that it is absorbed in a not completely satisfactory way, what presently makes it as such unsuitable for practical oral administration: also, at present no salt or ester derivatives of FCE 22250 which may be hydrolized in the organism after absorption are known.
This problem has been taken into very careful consideration and it has been found that the bioavailability and water solubility of FCE 22250 in an environment with a pH from substantially neutral to about 1 (as it is in the gastrointestinal tract of animals) are rather low: this may explain why FC 22250 is unsatisfactorily absorbed when it is administered by oral route.
It has now been surprisingly discovered that the oxidized (quinone) derivative of FCE 22250, which is the 3-(N-piperidinomethyl-azino)methylrifamycin S (labelled by the patentees as FCE 22807) is provided with a surprisingly high water solubility and enhanced bioavailability with reference to its reduced parent compound (FCE 22250). Thus, FCE 22807 is well suited for oral administration. It is also well known that in the organs of animals (especially in the liver) there are enzymes transforming oxidized compounds into the corresponding reduced compounds and vice-versa. It might so be that FCE 22807 gets wholly or partially metabolized into the parent reduced FCE 22250.
The title compound, 3-(N-piperidinomethylazino)methylrifamycin S (FCE 22807) and its synthesis were already described at the end of Example 1 of the cited U.S. Pat. No. 4,447,432, where such a product was identified by its MS and Rf characteristics.
Nothing however was said or was obvious for one skilled in the art for leaving to understand that the oxidized (quinone) FCE 22807 had a so enhanced solubility and bioavailability with reference to its parent reduced (hydroquinone) FCE 22250.
Indeed the very many works carried out in many Universities and laboratories throughout the world have always made use of the reduced FCE 22250 (see also IL FARMACO, May 1985, No. 5) and never of its parent FCE 22807.
US Referenced Citations (1)
| Number |
Name |
Date |
Kind |
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4447432 |
Franceschi et al. |
May 1984 |
|
Continuation in Parts (1)
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Number |
Date |
Country |
| Parent |
304033 |
Jan 1989 |
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Patent Grant
4956373
