Use of botulinum neurotoxin in the treatment of sialorrhea

Patent metadata

Field	Value
Publication number	US-11529398-B2
Application number	US-202016893799-A
Country	US
Kind code	B2
Filing date	Jun 5, 2020
Priority date	Mar 24, 2017
Publication date	Dec 20, 2022
Grant date	Dec 20, 2022

Abstract

This invention relates to improved uses of botulinum neurotoxins in the treatment of sialorrhea or diseases or conditions relating to increased saliva production. In particular are botulinum neurotoxins disclosed which are administered into parotid and submandibular glands in a dose ratio between 1.45 to 1 and 1.7 to 1.

First claim

The invention claimed is:

1. A method for treating a disease or condition associated with sialorrhea or increased saliva production in a patient, the method comprising administering a therapeutically effective amount of a botulinum neurotoxin by injection into the parotid glands and submandibular glands of the patient in at least four consecutive treatment cycles,
wherein the disease or condition is further associated with stroke, traumatic brain injury (TBI), clozapine induced hypersalivation, Rett syndrome, Angelman syndrome, epileptic encephalopathy, brain tumours, or intellectual disability,
wherein there is a time interval between the consecutive treatment cycles of between 14 and 18 weeks,
wherein each treatment cycle comprises administering the botulinum neurotoxin in a total dose between 1 and 2.5 U/Kg body weight, and the total dose of the botulinum neurotoxin administered into the parotid glands and submandibular glands is between 20 U and 75 U,
and wherein the ratio between the amount of the botulinum neurotoxin administered into each of the parotid glands and each of the submandibular glands is between 1.45 to 1 and 1.7 to 1.

2. The method according to claim 1 , wherein said botulinum neurotoxin is injected into one site of each submandibular gland and/or into one site of each parotid gland.

3. The method according to claim 1 , wherein the botulinum neurotoxin is injected into the parotid glands and submandibular glands using ultrasound guidance.

4. The method according to claim 1 , wherein said botulinum neurotoxin is a botulinum neurotoxin complex.

5. The method according to claim 1 , wherein said botulinum neurotoxin is the neurotoxic component of a botulinum neurotoxin complex, wherein said neurotoxic component is devoid of any other protein component of the Clostridium botulinum neurotoxin complex.

6. The method according to claim 1 , wherein said botulinum neurotoxin is selected from the group of botulinum neurotoxin serotypes consisting of botulinum neurotoxin serotype A, botulinum neurotoxin serotype B, botulinum neurotoxin serotype C1, botulinum neurotoxin serotype D, botulinum neurotoxin serotype E, botulinum neurotoxin serotype F and botulinum neurotoxin serotype G.

7. The method according to claim 1 , wherein the disease or condition is associated with stroke.

8. The method according to claim 1 , wherein the time interval is between 15 and 17 weeks.

9. The method according to claim 1 , wherein said botulinum neurotoxin is administered in an aqueous composition having a botulinum neurotoxin concentration of 25 U/mL.

10. The method according to claim 1 , wherein said botulinum neurotoxin is administered in 0.16 to 0.60 ml per injection site into the submandibular glands and in 0.24 to 0.9 ml per injection site into the parotid glands.

11. The method according to claim 1 , wherein the ratio between the amount of the botulinum neurotoxin administered into each of the parotid glands and each of the submandibular glands is between 1.5 to 1 and 1.6 to 1.

12. The method according to claim 1 , wherein the ratio between the amount of the botulinum neurotoxin administered into each of the parotid glands and each of the submandibular glands is 1.5 to 1.

13. The method according to claim 1 , wherein the time interval is 16 weeks.

14. The method according to claim 1 , wherein each treatment cycle comprises administering the botulinum neurotoxin in a total dose between 1.3 and 2.2 U/Kg body weight.

15. The method according to claim 1 , wherein the time interval is 15 weeks.

16. The method according to claim 1 , wherein the time interval is 17 weeks.

17. The method according to claim 1 , wherein the disease or condition is associated with traumatic brain injury (TBI).

18. The method according to claim 1 , wherein the disease or condition is associated with clozapine induced hypersalivation.

19. The method according to claim 1 , wherein the disease or condition is associated with Rett syndrome or Angelman syndrome.

20. The method according to claim 1 , wherein the disease or condition is associated with epileptic encephalopathy.

21. The method according to claim 1 , wherein the disease or condition is associated with brain tumours.

22. The method according to claim 1 , wherein the disease or condition is associated with intellectual disability.

Assignees

• Merz Pharma Gmbh & Co Kgaa

Inventors

• Csikos Janos
• Pulte Irena
• Althaus Michael
• Krueer Markus
• Wegener Nico

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K38/4893 Primary

  Botulinum neurotoxin (3.4.24.69) · CPC title