Botulinum toxin

Wrinkle injection with botulinum toxin (Botox for short) is a classic method of aesthetic medicine. It is used in particular to combat mimic wrinkles. Botox, a bacterial protein, specifically blocks nerve signals for muscle contraction. In very small quantities injected into the mimic musculature of the face with a very thin needle, the mimic musculature is weakened and existing wrinkles are reduced. Another field of application is the treatment of excessive sweat production (hyperhidrosis).

What is Botox®?

Botox stands for botulinum toxin (BTX) or botulinum neurotoxin (BoNT). Botox is a protein produced by the bacterium Clostridium botulinum. This bacterium produces eight different types of botulinum toxin (A, B, Cα, Cβ, D, E, F and G). Botulinum toxin A has the strongest effect. Botox has been used since 1980 to relax muscles, since 1990 to treat wrinkles and since 1996 to treat sweaty hands. Botulinum toxin was first approved by the US Food and Drug Administration in 2002 for the treatment of frown lines and forehead wrinkles. Botox has also been approved for the treatment of crow's feet since 2013. There are currently three FDA-approved products with botulinum toxin A for wrinkle treatment: Abobotulinum toxin A (Dysport®/Azzalure®), Onabotulinum toxin A (Botox®/Vistabel®) and Incobotulinum toxin A (Xeomin®/Bocouture®).

How does Botox® work?

In very low concentrations, it inhibits the signal transmission from the nerves to the muscles. The signal transmission takes place through the messenger substance acetylcholine. This messenger substance is not stored in any vesicles within the nerve switching points. When a nerve impulse reaches the musculature, the messenger substance acetylcholine is released from the vesicles like an air bubble that comes to the surface of the water. On the inner surface of the nerves, the botulinum toxin prevents the vesicles from reaching the surface. The vesicles thus remain suspended beneath the surface of the water. After a certain time, the nerve cells again form the protein required to open the vesicles (synaptosomal protein weighing 25 kilodaltons, SNAP-25 for short). Therefore, the effect of Botox gradually decreases. The effect of Botox unfolds within a certain radius around the injection point. The size of the treatment field is determined by the product properties, the dose administered and the volume as well as the injection technique. On a diameter of about one centimeter around the injection the muscles relax and the sweat gland production decreases.

What is the difference between Botox®/Vistabel®, Dysport®/Azzalure® and Xeomin®/Bocouture®?

The active ingredient in Dysport®/Azzalure® is called AbobotulinumtoxinA and is manufactured by the Paris-based pharmaceutical group Ipsen. Galderma, a Swiss pharmaceutical company based in Lausanne, acquired the exclusive rights to develop, market and distribute Dysport®/Azzalure® in Europe in 2007. Botox®/Vistabel® contains the active ingredient onabotulinum toxinA and is manufactured by the pharmaceutical group Allergan, headquartered in Irvine, California. The pharmaceutical company Merz Pharmaceuticals GmbH, headquartered in Frankfurt, manufactures Xeomin®/Bocouture® with the active ingredient IncobotulinumtoxinA. These products differ in terms of the manufacturing process and additives. All three products contain the A1 subtype of botulinum toxin A with a molecular weight of 150 kilodaltons. All three products contain human serum albumin. Botox® contains approx. 0.9 nanograms botulinum toxin A per 100 units, Dysport® contains 1.6 nanograms per 300 units and Xeomin® approx. 0.4 nanograms per 100 units. There are few good fact-based studies that show a significant difference between the three products. Dysport®/Azzalure® and Xeomin®/Bocouture® have an earlier onset of action than Botox®/Vistabel®. The effect of Dysport®/Azzalure® lasts somewhat longer compared to Botox®/Vistabel®. Dysport®/Azzalure® and Botox®/Vistabel® should be stored at temperatures below eight degrees Celsius and Xeomin®/Bocouture® at temperatures below twenty-five degrees.

What is a Botox® unit?

A Botox unit is a quantity. The unit of botulinum toxin was defined in laboratory tests and is abbreviated as "E". Since the test conditions were not defined down to the smallest detail, the units differ from one manufacturer to another. Botox units are specific to each product and are not interchangeable. For example, the following dosages are recommended for the treatment of frown lines: Dysport®/Azzalure® 50 E, Botox®/Vistabel® 20 E, and Xeomin®/Bocouture® 20 E.

How long does a Botox treatment last?

The effect already occurs after two days. Ninety percent of patients experience a clear effect on the seventh day. The maximum effect occurs on the fourteenth day. The onset of the effect depends, among other things, on the product, the dosage and the injection technique. On average, the effect lasts four months. In one third of patients, a satisfactory effect can still be demonstrated after five months. A repetition of the treatment therefore makes sense at the earliest after three months. After several treatments, the duration of effect can be prolonged, as the cross-section of the relaxed muscles is reduced.

Can I become immune to Botox® treatments?

The organism can develop different antibodies. Only neutralizing antibodies can lead to a loss of efficacy. Very small amounts of Botox are required for the treatment of crow's feet. In addition, a repetition of the treatment is only necessary after a longer period of time. The risk of developing neutralising antibodies is therefore very low. In the world literature only very few cases have been described in which patients have developed neutralizing antibodies after an aesthetic treatment. Some patients do not respond well to Botox treatment. This may be due to inadequate dosing, improper storage or preparation, or incorrect injection technique.

Author's statement

Author: Stéphane Stahl, MD, PhD. There are no financial relationships with the pharmaceutical or medical device industries that could have influenced the above text. Any reproduction, even partial, is permitted for personal use only. All texts used on this website are protected by copyright.

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