Transdermal botulinum toxin compositions

• US 9,144,692 B2
• Filed: 10/30/2007
• Issued: 09/29/2015
• Est. Priority Date: 07/11/2002
• Status: Expired due to Fees

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Donovan, Stephen
• Primary Examiner(s): Minnifield, Nita M
• Application Number:
  US11/929,871
• Publication Number:
  US 20080220020A1
• Time in Patent Office: 2,891 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 38/4893 Botulinum neurotoxin (3.4.24.69)
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Pharmaceutical compositions for transdermal administration of neurotoxins to a patient include a neurotoxin, such as a botulinum toxin, and an enhancing agent that facilitates absorption of the neurotoxin through the skin of the patient and does not eliminate the bioactivity associated with the neurotoxin. The pharmaceutical compositions are topically applied on a patient, and may be provided in a transdermal patch.

Claims

1. A transdermal patch comprising:

a pharmaceutical composition comprising a stabilized botulinum toxin provided in a dried state; and

at least one enhancing agent that is mixable with the stabilized botulinum toxin provided in a dried state for facilitating transdermal delivery of the botulinum toxin into a human patient by enhancing the permeability of the patient'"'"'s skin, and

an adhesive layer disposed to one side of the transdermal patch to removably secure the patch on the human patient'"'"'s skin;

wherein the pharmaceutical composition is incorporated into the adhesive layer, and wherein the adhesive layer is heat activated such that at a temperature of about 37 degrees Celsius the adhesive layer slowly liquefies to facilitate diffusion of the pharmaceutical composition through the skin.

2. The composition of claim 1, wherein the botulinum toxin is selected from the group consisting of botulinum toxin types A, B, C₁, D, E, F and G.

3. The composition of claim 1, wherein the botulinum toxin is botulinum toxin type A.

4. The composition of claim 1, wherein the botulinum toxin is a purified botulinum toxin.

5. The composition of claim 1, wherein the composition comprises an amount of botulinum toxin to achieve a therapeutic effect lasting between 1 month and 5 years.

6. The composition of claim 1, further comprising an additional enhancing agent and wherein the enhancing agent is an alcohol.

7. The composition of claim 6, wherein the alcohol is a polyalcohol.

8. The composition of claim 1, wherein the enhancing agent comprises a transferosome.

9. The composition of claim 1, wherein the composition comprises a plurality of enhancing agents.

10. A pharmaceutical composition in a transdermal patch, the pharmaceutical composition comprising a stabilized botulinum toxin provided in a dried state in a first pocket sealed with a dissolvable membrane, the dried botulinum toxin is mixable and solubilizable with an enhancing agent provided in a rupturable second pocket in the transdermal patch to allow the pharmaceutical composition to permeate through a human patient'"'"'s skin without permeating in significant amount through a blood vessel.

11. The composition of claim 10 wherein the dissolvable membrane dissolves upon contacting a fluid.

12. The composition of claim 10, wherein the botulinum toxin is botulinum toxin type A.

13. The composition of claim 10, wherein the rupturable second pocket is ruptured by pressure exerted on the patch.

14. The composition of claim 13, wherein the enhancing agent is an alcohol.

15. A transdermal patch, comprising:

a pharmaceutical composition, which comprises a stabilized botulinum toxin, the botulinum toxin is incorporated in a polymeric matrix that stabilizes the botulinum toxin; and

an enhancing agent that facilitates transdermal administration of the botulinum toxin; and

an adhesive disposed on one side of the transdermal patch to removably secure the patch to the patient'"'"'s skin, wherein the pharmaceutical composition is incorporated into the adhesive layer, and wherein the adhesive layer is heat activated such that at a temperature of about 37 degrees Celsius the adhesive layer slowly liquefies to facilitate diffusion of the pharmaceutical composition through the skin, and

a plurality of needles extending from a dermal surface of the transdermal patch, the needles ranging from about 20 micrometer to about 1 millimeter long.

16. The transdermal patch of claim 15, wherein the adhesive is disposed around a depot containing the pharmaceutical composition.

17. The transdermal patch of claim 15, wherein the plurality of needles extending from one side of the patch that is applied to the skin, wherein the needles extend from the patch to project through the stratum corneum of the skin without rupturing a blood vessel.

18. The transdermal patch of claim 17, wherein the botulinum toxin is provided in a depot in the patch so that pressure applied to the patch causes botulinum toxin to be directed through the needles and under the stratum corneum.

19. The transdermal patch of claim 15, wherein the botulinum toxin is provided in a dry state in a plurality of wells, each of the wells covered by a membrane that is dissolvable with a fluid, and wherein the enhancing agent mixes with the botulinum toxin as the membrane over a well dissolves so that the absorption of the botulinum toxin is enhanced.

20. The transdermal patch of claim 15, wherein the botulinum toxin is botulinum toxin type A.

21. The transdermal patch of claim 15, wherein the botulinum toxin is a purified botulinum toxin.

22. The transdermal patch of claim 15, wherein the composition comprises an amount of botulinum toxin to achieve a therapeutic effect lasting between 1 month and 5 years.

23. The transdermal patch of claim 15, wherein the enhancing agent is an alcohol.

24. The transdermal patch of claim 15, wherein the botulinum toxin is provided in a dry state in the transdermal patch before the patch is applied to the patient'"'"'s skin.

25. The transdermal patch of claim 15, further comprising a fluid disposed in one or more wells.

26. The transdermal patch of claim 25, wherein the fluid includes the enhancing agent.