1. Field of the Invention
The present invention relates to a lyophilized preparation of botulinum toxin without a protein stabilizer derived from animals.
2. Discussion of Related Art
Botulinum toxin, which is a polypeptide product of Clostridium botulinum, anaerobic bacteria, is a toxic material that specifically affects a nerve cell. Although botulinum toxin originally is a toxic material causing death, in recent years, it is used for treating cervical dystonia, blepharospasm, hyperhidrosis, strabismus, achalasia, neurogenic bladder, urologic disease, migraine, and the like. As an example of use of botulinum toxin as a pharmaceutical composition, there is Meditoxin Inj. being sold by the present inventors now.
Many proteins having a medicinal effect exhibit a property of adhesiveness to a solid surface. Therefore, when the proteins are injected to a container, some of the proteins adhere to an inner wall of the container, thereby causing loss of an active component. In addition, since protein may easily be oxidized or degraded into small fragments, it is necessary to add a stabilizer as a material capable of preventing oxidation and degradation of the protein.
Recently, albumin and gelatin are used as a stabilizer for botulinum toxin. Loss of protein active components may be decreased by reducing protein denaturation caused due to protein adhesion or dilution when albumin is injected into a container. Gelatin is obtained by collagen hydrolysis and sometimes may be used instead of albumin. However, since albumin and gelatin are proteins derived from animals, there is a danger of pathogens derived from blood or latent infection. Therefore, a stabilizer which is not derived from animals and also does not cause activity loss of botulinum toxin is needed.
In this regard, the present inventors disclosed a pharmaceutical liquid composition of botulinum toxin including botulinum toxin, methionine, and polysorbate 20 that exhibits long-term stability at normal temperature in Korean Patent Publication No. 2009-0005963. However, in such a liquid composition, it is difficult to maintain stability of botulinum toxin at a high temperature higher than normal temperature.