PHARMACEUTICAL COMPOSITIONS FOR TOPICAL USE CONTAINING MIOCAMYCIN

Abstract: The topical administration of the macrolide anti­ biotic miocamycin is proposed for the therapy of infections (caused by microbial flora sensitive to said antibiotic) of the skin and of the mucous membranes, this antibiotic being administered in suitable pharmaceutical forms such as ointment, globuli, ophthalmic ointment and mouthwash.

Description: The invention relates to the preparation of pharmaceutical forms containing miocamycin for topical administration (ointment, gel, globuli, ophthalmic ointment, and mouthwash), for the therapy of bacterial infections of the skin and of the mucous membranes (conjunctival, oropharyngeal, and vulvo-vaginal-cervical). The antibiotic therapy of bacterial infections of the skin and of the mucous membranes, as well as those dermatological disorders in which a microbial etiological aspect is involved (for example, acne), makes use, depending upon the particular cases involved, not only of the systemic administration route but also - and on occasions exclusively - of the topical administration route. Various chemo-antibiotics such as tetracyclines, aminoglycosides, chloramphenicol, are, in fact, widely used via the topical route. Miocamycin, a macrolide antibiotic with a spectrum of action such as to justify the use thereof in the infections set forth above (Yoshida et al., Jap. J. Antibiotics 135, 1462, 1982), although representing, as compared with other pharmaceutical products, an advantageous alternative both on account of the high degree of efficacy and on account of the excellent tolerability, has, to date, never been used for topical administration in the case of the abovementioned disorders. GB-A-2132086 discloses oral preparations of macrolide antibiotics, and in particular also of miocamycin. These oral preparations, however, are not suitable for administration through the topical route. In particular, no pharmaceutical forms containing excipients suitable for absorption through the skin are described. Rather, solid (granular) pharmaceutical forms suitably stabilized for enhancing bioavailability when administered through the oral route are disclosed. According to Martindale (Extra Pharmacopoeia 1982, page 1185 and page 1158), miocamycin is closely related to midecamycin, midecamycin has actions similar to those of erythromycin, and topical pharmaceutical forms like ointments and ophtalmic ointments having erythromycin as an active principle are known. The invention refers to a stable pharmaceutical composition containing miocamycin as active principle, and a carrier suitable for topical administration, for the therapy of bacterial infections of the skin and of the mucous membranes. In order to have a composition stable for a long period of time, the composition does not contain water. In those cases, such as mouthwash or gel forms, in which water is added to the composition, this is done only at the time of use. Examples of the formulation of various pharmaceutical forms according to the invention for topical administration, are given herein below: Example 1 An oinment having the following composition, related to 100 g: Example 2 The pharmaceutical form is a gel and consists in a suitable bottle containing the excipient and provided with a reservoir cap containing the active principle to be combined with the excipient at the time of use. This is due to the poor stability of the active principle over a long period of time in the presence of water; the gel thickens on being administered to the tissues at body temperature. The composition is the following, related to 100 g: Content of the bottle: Example 3 Globuli having the following unit composition: Example 4 Globuli having the following unit composition: Example 5 Mouthwash consisting of granules in a single-dose package, to be suspended in water at the time of use, and having the following unit composition: Example 6 Ophthalmic ointment having the following composition per 100 g:

Claims: Claims for the following Contracting States : AT, BE, CH, DE, FR, GB, LI, LU, NL, SE 1. A stable pharmaceutical composition containing miocamycin as active principle and a carrier suitable for topical administration, in the absence of water, for the therapy of bacterial infections of the skin and of the mucous membranes (conjunctival, oropharyngeal, and vulvo-vaginal-cervical). 2. The composition as claimed in claim 1 in ointment form, having a formulation as follows, related to 100 g: 3. The composition as claimed in claim 1, in the form of globuli having the following unit formulation: 4. The composition as claimed in claim 1, in the form of globuli having the following unit formulation: 5. The composition as claimed in claim 1, in the form of an ophthalmic ointment having the following formulation per 100 g: 6. A pharmaceutical composition, containing miocamycin as an active principle for topical administration in the form of mouthwash, consisting of granules in a single-dose packet, to be suspended in water at the time of use, having the following unit formulation: 7. A pharmaceutical composition containing miocamycin for topical administration for the therapy of bacterial infections of the skin and of the mucous membranes consisting in a bottle containing water and a gelling agent, and a cap containing the miocamycin as active principle, the active principle being mixed with the content of the bottle at the time of use. 8. The composition as claimed in claim 7, having a formulation as follows, related to 100 g: Content of the bottle: Claims for the following Contracting States : GR, ES 1. Method for the preparation of a stable pharmaceutical composition containing miocamycin as active principle, wherein the active principle is added to a carrier suitable for topical administration, in the absence of water, for the therapy of bacterial infections of the skin and of the mucous membranes (conjunctival, oropharyngeal, and vulvo-vaginal-cervical). 2. The method as claimed in claim 1, for the preparation of an ointment having a formulation as follows, related to 100 g: 3. The method as claimed in claim 1, for the preparation of a pharmaceutical composition in form of globuli having the following unit formulation: 4. The method as claimed in claim 1, for the preparation of a pharmaceutical composition in the form of globuli having the following unit formulation: 5. The method as claimed in claim 1, for the preparation of a pharmaceutical composition in the form of an ophthalmic ointment having the following formulation per 100 g: 6. A method for the preparation of a pharmaceutical composition, containing miocamycin as an active principle, wherein the active principle is added to a carrier suitable for topical administration, in the form of a mouthwash, consisting of granules in a single-dose packet, to be suspended in water at the time of use, having the following unit formulation: 7. A method for the preparation of a pharmaceutical composition containing miocamycin as the active principle, suitable for topical administration for the therapy of bacterial infections of the skin and of the mucous membranes, wherein the active principle is inserted in a cap of a bottle, the bottle containing water and a gelling agent, the active principle being mixed with the content of the bottle at the time of use. 8. The method as claimed in claim 7, for the preparation of a composition having a formulation as follows, related to 100 g: Content of the bottle:

Inventors: BANI, RAFFAELLO, CARLESI, ROBERTO MASSIMO, GHELARDONI, MARIO, MELANI, FRANCESCO
Applicants: A. MENARINI INDUSTRIE FARMACEUTICHE RIUNITE S.R.L.
Application year: 1988
Main classification: A61K31
IPC codes: A61K9, A61P31, A61K47, A61P27, A61K31, A61P17