Title:  Therapeutic agent for the suppression of snoring noises

United States Patent:  6,573,241

Issued:  June 3, 2003

Inventors:  Bigalke; Hans (Hannover, DE); Frevert; Jurgen (Berlin, DE)

Assignee:  BioteCon Gesellschaft fur bio-technologische Entwicklung und Consulting (Berlin, DE)

Appl. No.:  857835

Filed:  June 8, 2001

PCT Filed:  December 10, 1999

PCT NO:  PCT/EP99/09791

PCT PUB.NO.:  WO00/33863

PCT PUB. Date:  June 15, 2000

In a method of manufacturing a therapeutic agent to be administered intramuscularly for suppressing snoring noises a high-purity Clostridium toxin BoNT/A or TeNT or at least one of a high-purity Clostridium toxin BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F and BoNT/G is added to a carrier. In an alternative, one or more hybrid proteins as a Clostridium toxin, having a light subunit of a Clostridium toxin of the following group and a heavy subunit of a different Clostridium toxin of the same following group, which group contains BoNT/A, BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F, BoNT/G and TeNT, are added to a carrier. According to another alternative, a complex, containing a Clostridium toxin or a hybrid protein, and further containing one or more therapeutically well-tolerated hemagglutinins and/or pharmaceutically well-tolerated non-toxic proteins, is added to a carrier. The carrier can be an aqueous solution, a saline solution, or liposomes.

SUMMARY OF THE INVENTION

An elimination of snoring could be achieved if it were possible to suppress the increased tone of the palate muscles in the deep sleep phase. Since the tone increase is caused by an increased acetylcholine release, the blockage of the release can cause the muscles to relax and can eliminate snoring.

The object of the invention is now solved by therapeutic agents for suppressing snoring noises which are characterized by a Clostridium toxin and/or a complex of this toxin or a contents of toxin or complex.

Accordingly, the invention relates to a therapeutic agent for suppressing snoring noises which is characterized by a high-purity Clostridium toxin BoNT/A.

Accordingly, BoNT/A can be injected in minimal dosage into the respective muscle of the soft palate, for example, into the M. tensor veli palatini. With the same injection technology the spasmodic dysphonia is already treated which is also the result of an increased tone of certain muscles of the soft palate (Schonweiler et al., 1998).

Moreover, the invention concerns a therapeutic agent for suppressing snoring noises which is characterized by a high-purity Clostridium toxin BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F and/or BoNT/G.

Moreover, the invention relates to a therapeutic agent for suppressing snoring noises which is characterized by a high-purity Clostridium toxin TeNT.

Moreover, the invention relates to a therapeutic agent for suppressing snoring noises, which is characterized by

(i) a hybrid protein as the Clostridium toxin, comprised of a light subunit of a Clostridium toxin of the following group and of a heavy subunit of a different Clostridium toxin of the same following group, comprised of: BoNT/A, BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F, BoNT/G and TeNT; or

(ii) by a mixture of hybrid proteins according to (i).

Moreover, the invention relates to a therapeutic agent which is characterized by a complex, comprising

(i) a Clostridium toxin or a hybridprotein and

(ii) one or more therapeutically well-tolerated hemagglutinins and/or one or more pharmaceutically well-tolerated non-toxic proteins.

Moreover, the invention relates to a therapeutic agent which is characterized by a complex of the wild type.

Moreover, the invention relates to a therapeutic agent which is characterized in that the Clostridium toxin is a recombinant protein.

Moreover, the invention relates to a therapeutic agent which is characterized in that the Clostridium toxin is a lyophilized protein.

Moreover, the invention relates to a therapeutic agent which is characterized in that it is present as an aqueous solution, in particular, an aqueous injection solution.

Moreover, the invention relates to a therapeutic agent which is characterized in that the Clostridium toxin or its complex is present as a physiological saline solution.

Finally, the invention relates to a therapeutic agent which is characterized by liposomes as carriers for the Clostridium toxin or its complex.

The administration of the pure neurotoxin is preferred as compared to the injection of the complex because only the neurotoxin provides the activity. Since the neurotoxin has a smaller molecular weight than the complex, it is distributed by diffusion more quickly within the muscle tissue, binds on receptors, and inhibits the acetylcholine release after it has been endocyted by the nerve end. The other body-foreign proteins would have no own effect with respect to muscle paralysis. However, they would contribute to the stimulation of the immune system because they act as immune adjuvants and enhance the immune reactions. A stronger immune response is desired for inoculations. In the case of a therapeutic agent against snoring, however, an immune reaction could result in the undesirable formation of antibodies which would neutralize the toxin before it could become active in the case of a renewed dosage.

All body orifices, and thus also the nose-throat area, are rich in lymphatic tissue which protects the entryways against damaging substances. When injuries occur and body-foreign substances penetrate in this area, macrophages are attracted which endocyte the foreign substances, digest them and excrete the fragments of the foreign substances with cell-own proteins on their cell surface. In the spleen and other lymphatic tissues, lymphocytes detect the fragments and form immunoglobulins which bind foreign substances freely contained in the tissue and neutralize it.

The degree of attraction of the macrophages depends inter alia on the concentration of foreign substances and the availability of macrophages. The availability of macrophages cannot be influenced, and the palate area is rich in these cells. In order to keep the probability of an immune response minimal, the mass of foreign proteins, i.e., neurotoxin and hemagglutinins must be kept as minimal as possible because macrophages which are attracted in large numbers by non-active foreign substances (immune adjuvants) will, of course, also endocyte the neurotoxin present within the tissue. The mass of the neurotoxin can be reduced by a BoNT with high biological activity to a barely still active dosage. Because the accompanying proteins do not contribute to the desired effect, they can be removed in accordance with the invention.

Claim 1 of 16 Claims

What is claimed is:

1. A method of temporarily suppressing snoring noises, the method comprising the step of administering intramuscularly an effective amount of uncomplexed Clostridium toxin BoNT/A (botulinum neurotoxin type A) added to a carrier, thereby reducing the snoring.
 

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.