Prophylactic, therapeutic, systemic & topical treatment of acne and some of their drawbacks
A number of treatments are presently known for treating acne, some more successful than others. There are two modes of treatment, topical and systemic.
Ssome systemic treatments for acne that are presently employed are: oral tetracycline; oral erythromycin; minocycline; doxycycline; oral trimethoprim-sulfamethoxazole and isotretinoin. Those that have been suggested in the past and that are no longer generally employed include: antibacterial vaccines; estrogen therapy; dietary restrictions; and vitamin therapy (e.g. oral ingestion of vitamin A).
Some of the topical treatments that are presently employed are: topical erythromycin, clindamycin, benzoyl peroxide, 2% sulfur, 3% resorcinol, a tetracycline derivative (meclocycline sulfosalicylate 1%), 2% salicylic acid, and tretinoin. Topical treatments that have been suggested in the past and that are no longer generally employed include: x-ray treatment; electric sparks; vitamin therapy.
More specifically with respect to the topical use of certain specific antibiotics, a topical solution, ointment, and gel containing erythromycin is used. Also used is a topical solution, gel, and lotion containing clindamycin, and a cream containing meclocycline sulfosalicylate 1% (a tetracycline derivative).
Some of the undesirable side effects of orally administered antibiotics are abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth, loss of appetite, nausea, vomiting, fever, hearing loss, jaundice, rash, rectal and vaginal itching, and superinfection.
It is noted that erythromycin is produced by the bacterium Streptomyces erytheus and that erythromycin has a chemical structure that is substantially unique to erythromycin and its derivatives. The molecular weight of erythromycin A is 733.92. The empirical formula for erythromycin A is C.sub.37 H.sub.67 NO.sub.13 having a 60.55% carbon content, a 9.20% hydrogen content, a 1.91% nitrogen content, and a 28.34% oxygen content.
Clindamycin has a chemical structure indicated by its chemical name which is methyl 7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]ami no]-1-thio-L-threo-alpha-D-g alacto-octopyranoside. The molecular weight of clindamycin is 424.98. The empirical formula for clindamycin is C.sub.1 H.sub.337 ClN.sub.2 O.sub.5 S having a 50.87% carbon content, a 7.83% hydrogen content, a 8.34% chlorine content, a 6.59% nitrogen content, a 18.82% oxygen content, and a 7.54% sulfur content.
Other topical treatments for acne using antibiotics are described in the following Great Britain patents: neomycin, G. B. Pat. No. 1,054,124; erythromycin, G. B. Pat. No. 1,587,428; and erythromycin derivatives in conjunction with benzoyl peroxide, G. B. Pat. Nos. 2,088,717 and 2,090,135.
Still other topical treatments for acne using anti-bacterials are described in the following U.S. patents: an azole derivative in conjunction with benzoyl peroxide, U.S. Pat. No. 4,446,145, incorporated herein by reference; and metronidazole in a special gel as described in U.S. Pat. No. 4,837,378, incorporated herein by reference.
The etiopathology of acne, although unclear, starts in formation of a characteristic lesion: the comedo. This produces a blockage in the pilosebaceous canal following dyskeratinization of the infundibular zone of the canal. A major effect of the blockage is to modify the rheology of the sebum and the physicochemical properties of the area. Such modification allows resident cutaneous strains to hyperproliferate which in turn triggers an inflammation reaction in the organism.
Benzoyl peroxide has been known for several years to be a particularly interesting keratolytic agent among recognized therapeutic acne treatments. In addition, it has good bacteriostatic properties.
Use of standard antibiotics in acne treatment is also widespread. They do, in fact, shown considerable bacteriostatic and anti-inflammatory activity. Orally administered active antibiotics are numerous. Among these, clindamycin and especially erythromycin show topical activity.
Antibiotics have previously been combined with benzoyl peroxide in order to increase the activity of topical anti-acne compositions. In particular, erythromycin has already been combined with benzoyl peroxide.
However, a major drawback of the use of antibiotics (either alone or in combination with benzoyl peroxide) lies in their prolonged use whereupon bacterial flora become resistant, rendering the antibiotics less effective in subsequent treatment.
Further, benzoyl peroxide-erythromycin combinations are unstable over periods of time.
Quaternary ammonium compounds have been envisaged as replacements for antibiotics in topical treatment of acne. It has been shown that certain quaternary ammonium compounds are as effective as antibiotics against the main strains responsible for acne, without inducing resistance.
In such compositions, benzoyl peroxide acts by decomposing to liberate active oxygen in situ. Compositions which comprise benzoylperoxide as an active ingredient, are considered to be amongst the most effective ones in the treatment of acne vulgaris.
To improve the effect of benzoylperoxide there are frequently added to the compositions other known anti-acne substances. For example, there is a substantial increase in the therapeutic effect when benzoylperoxide is used in combination with retinoic acid.
Considerable disadvantages of such compositions are, however, that they frequently cause allergic contact dermatitis and/or that they are, in certain cases, extremely irritating and drying, necessitating alteration of either the frequency or the duration of the applications or the concentration of the active ingredients in the composition.
Especially in the treatment of patients with inflammatory lesions, benzoylperoxide is often used in combination with orally administered antibiotics, e.g., tetracycline, erythromycin and the like. However, many questions have been raised concerning the safety of short- and long term use of orally administered antibiotics in the treatment of acne.
Moreover, as a general rule, it is desirable to avoid oral therapy in the treatment of skin diseases whenever an effective topical treatment modality is available.
Last modified: June 26, 2009
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