Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
2001-12-11
2004-12-21
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C514S152000, C514S199000, C514S311000, C514S826000
Reexamination Certificate
active
06833389
ABSTRACT:
The present invention relates to the use of thiamphenicol and derivatives thereof for the preparation of pharmaceutical compositions useful in the treatment of
Chlamydia pneumoniae
infections.
Chlamydia pneumoniae
is an intracellular bacterium recently considered responsible of respiratory infections both of the upper tract and the lower tract.
This bacterium is one of the most widespread human pathogens and primary infections in children from 5 to 14 years have been supported by documentary evidence. In children the infection is generally mild and asymptomatic, but can be more serious in adult and elderly.
Chlamydia pneumoniae
is responsible for about 10% of cases of atypical pneumonia and of 5% of cases of bronchitis. It has also been associated with respiratory airways diseases and with new onset asthma and asthmatic bronchitis in the adults. Sinusitis caused by
Chlamydia pneumoniae
also associated with infections of the lower respiratory tract has been described and, moreover,
Chlamydia pneumoniae
has been isolated from middle ear fluids of patients with otitis media.
For a survey of the pathologies associated to
Chlamydia pneumoniae
infections see F. Blasi, Clinical Microbiology and Infections, vol. 1, Suppl. 1, March 1996, S14-S18.
Among the antibiotics more commonly used in therapy, azithromycin and, in particular, clarithromycin resulted active in vitro against
Chlamydia pneumoniae
and others agents involved in these infections and therefore they are potential therapeutical agents in the treatment of
Chlamydia pneumoniae
infections.
Some quinolonic antibiotics too, offer a potential therapy for
Chlamydia pneumoniae
infections.
In the cases of
Chlamydia pneumoniae
infection the antibiotic treatment can require a long period and cases of
Chlamydia pneumoniae
chronic persistent infections in which the antibiotic therapy has failed have already been reported.
The restricted number of antibiotics useful in the treatment of
Chlamydia pneumoniae
infections and the increasing importance that these infections are assuming from a clinical point of view, make necessary the identifying of antibiotics active against
Chlamydia pneumoniae
. Thiamphenicol (The Merck Index, XII ed., No. 9436, page 1587) is a known antibiotic used for the treatment of Gram-positive and Gram-negative bacterial infection. In the treatment of respiratory pathologies thiamphenicol is often used as glycinate hydrochloride or acetylcysteinate, i.e. an ester of thiamphenicol salified with hydrochloric acid or with acetylcysteine respectively.
To our knowledge no data concerning the activity of thiamphenicol or derivatives thereof versus
Chlamydia pneumoniae
is reported in the literature. It is known instead that thiamphenicol is active against
Chlamydia trachomatis
, a pathogen responsible of urogenital apparatus infections, but its activity is markedly lower than that of other antibiotics, such as for example erythromycin [G. Ridgeway et al., J. Antimicrob. Chemother. (1979), 5(4), 483-4]. We have now found that thiamphenicol is particularly effective in the treatment of infections caused by
Chlamydia pneumoniae.
It is therefore an object of the present invention the use of thiamphenicol and derivatives thereof for the preparation of a pharmaceutical compositions useful in the treatment of
Chlamydia pneumoniae
infections.
The pharmaceutical compositions useful in the present invention are compositions for enteral or parenteral use containing thiamphenicol or derivatives thereof such as, for example, thiamphenicol glycinate and salts thereof.
Particularly preferred is the use of thiamphenicol glycinate acetylcysteinate.
Also preferred is the use of thiamphenicol glycinate hydrochloride.
The amount of active ingredient, expressed as thiamphenicol, contained in the pharmaceutical composition may change depending on the administration way and on the seriousness of the infection but is generally comprised between 250 mg and 5000 mg per dose, more preferably between 500 mg and 2000 mg.
The pharmaceutical compositions can be in a solid or liquid form, suitable for administering by injectable, oral or aerosol route.
Preferred are the pharmaceutical compositions suitable for administering by aerosol or injectable route.
More preferred are the pharmaceutical compositions suitable for administering by aerosol or injectable route containing thiamphenicol glycinate hydrochloride or acetylcysteinate.
Particularly suitable are the pharmaceutical compositions already on the market with the trademark FLUIMUCIL ANTIBIOTICO® and GLITISOL®.
The thiamphenicol efficacy against strains of
Chlamydia pneumoniae
of recent clinical isolation has been demonstrated in vitro by calculating the MIC (Minimum Inhibitory Concentration) in comparison with other antibiotics. It is important to underline as thiamphenicol showed a MIC completely comparable, or better, with respect to that of reference antibiotics already used in therapy for the treatment of
Chlamydia pneumoniae
infections.
With the aim to better illustrate the present invention the following example is now given.
REFERENCES:
patent: 3691229 (1972-09-01), Della Bella et al.
patent: 6589993 (2003-07-01), Ungheri et al.
patent: 00 01378 (2000-01-01), None
Budavari et al., The Merck Index, Twelfth Edition (1996), pp. 1587, abstract No. 9436.*
Jack M. Bernstein, MD, “Treatment of Community-Acquired Pneumonia—IDSA Guidelines,” Chest/115/3/Mar., 1999.
Murat V. Kalayoglu, MD, PhD, et al., “Chlamydia pneumoniaeas an Emerging Risk Factor in Cardiovascular Disease,” American Medical Association, JAMA, vol. 288, No. 21, Dec. 4, 2002.
L. Richaldl, et al., “Macrolldes for chronic asthma,” The Cochrane Library 2003, Issue 1, pp. 1-16.
“Practice guidelines for the management of community-acquired pneumonia in adults,” Bibliographic Source(s)—Bartlett JG, et al., Clin Infect Dis 2000 Aug.; 31 (2), pp. 1-10.
Alessandra Lombardi et al.; “Antimicrobial activity of thiamphenicol-gycinate-acetylcysteinate and other drugs against Chlamydia pneumoniae” Arzeimittel-Forschung, vol. 51, No. 3, pp. 264-267, 2001.
F. Blasi: “Clinical features of chlamydia pneumoniae acute respiratory infection” Clinical Microbiology and Infection, vol. 1, pp. s14-s18, Mar. 1, 1996.
Colombo Giovanni Battista
Drago Lorenzo
Gismondo Maria Rita
Licciardello Luciano
Ungheri Domenico
Weddington Kevin E.
Zambon Group S.p.A.
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