Heat assisted lidocaine and tetracaine for transdermal analgesia

• US 9,186,334 B2
• Filed: 03/16/2011
• Issued: 11/17/2015
• Est. Priority Date: 05/04/2009
• Status: Expired due to Fees

• Current Assignee: Nuvo Pharmaceuticals Inc. (Searchlight Pharma, Inc.)
• Original Assignee: Nuvo Research AG (Searchlight Pharma, Inc.)
• Inventors: Zhang, Jie, Lippert, Robert
• Primary Examiner(s): RICCI, CRAIG D
• Application Number:
  US13/049,650
• Publication Number:
  US 20120065259A1
• Time in Patent Office: 1,707 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61F 2007/0071 using a resistor, e.g. near the spot to be heated
• CPC Class Codes: A61F 2007/0226 adhesive, self-sticking
• CPC Class Codes: A61F 2007/0257 with a fluid impermeable layer
• CPC Class Codes: A61F 2007/0261 medicated
• CPC Class Codes: A61F 2007/0292 using latent heat produced or absorbed during phase change of materials, e.g. of super-cooled solutions
• CPC Class Codes: A61F 7/02 Compresses or poultices for effecting heating or cooling
• CPC Class Codes: A61F 7/034 Flameless
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

The present disclosure is drawn to methods for treating various types of pain, including pain associated nerve entrapment, neuroma, headaches, connective tissue, arthritis, injury, and/or overuse. Specifically, the method includes the application of an analgesic system to a skin surface of a subject experiencing the pain and maintaining the analgesic system on the skin surface for an application period of at least 30 minutes. Following the application period the analgesic system can be removed and the subject being treated continues to experience reduction of pain for a period of 2 to 10, or even 4 to 12 hours after removal of the analgesic system. The analgesic system applied to the skin surface can include a heating component and a local anesthetic formulation.

Claims

1. A method for treating an existing pain selected from the group consisting of nerve entrapment pain, neuroma pain, headache pain, connective tissue pain, arthritis pain, pain associated with injury, pain associated with overuse, and combinations thereof, comprising:

a) applying at least one integrated analgesic system to a skin surface of a subject experiencing pain, said analgesic system comprising;

i) a heating device configured to heat the skin surface to a temperature of 35°

C. to 47°

C., and

ii) a local anesthetic formulation including a eutectic mixture of lidocaine and tetracaine, wherein the local anesthetic formulation is applied to the skin surface over the existing pain;

b) heating the skin surface to a temperature of 35°

C. to 47°

C.; and

c) maintaining the analgesic system on the skin surface for an application period of at least 2 hours.

2. The method of claim 1, wherein the eutectic mixture comprises at least 30 wt % of the local anesthetic formulation.

3. The method of claim 1, wherein the eutectic mixture comprises at least 10 wt % of the local anesthetic formulation.

4. The method of claim 1, wherein the local anesthetic formulation has a skin contact area having an area of 2 cm² to 200 cm².

5. The method of claim 1, wherein the local anesthetic formulation has a skin contact area from 5 cm² to 130 cm².

6. The method of claim 1, wherein the local anesthetic formulation has a skin contact area from 8 cm² to 40 cm².

7. The method of claim 1, wherein the existing pain is an acute pain.

8. The method of claim 1, wherein the subject begins experiencing a reduction of existing pain within 1 hour of application of the analgesic system.

9. The method of claim 1, wherein the subject begins experiencing a reduction of existing pain within 30 minutes of application of the analgesic system.

10. The method of claim 1, wherein two or more analgesic systems are applied to a skin surface of a subject experiencing pain.

11. The method of claim 1, wherein the analgesic system is applied more than once a day.

12. The method of claim 1, wherein the analgesic system is applied as daily treatment for at least two weeks.

13. The method of claim 1, wherein the delivery of the local anesthetic formulation through the skin is more rapid than delivery of the local anesthetic formulation using an unheated patch.

14. The method of claim 1, wherein the reduction of pain includes a reduction in pain intensity and pain interference.

15. The method of claim 1, wherein the existing pain is pain associated with at least one of the head, neck, shoulder, knee, leg, ankle, hip, elbow or wrist.

16. The method of claim 1, wherein the eutectic mixture of lidocaine and tetracaine is at a weight ratio of 2:

1 to 1;

2.

17. The method of claim 1, wherein the heating device is configured to generate heat by an exothermic oxidative chemical reaction.

18. The method of claim 1, wherein the skin surface is heated to a temperature of 36°

C. to 42°

C.

19. The method of claim 1, wherein the skin surface is heated to a temperature of 38°

C. to 42°

C.

20. The method of claim 1, wherein the skin surface is heated to a temperature of 36°

C. to 40°

C.

21. The method of claim 1, further comprising removing the analgesic system after the application period, wherein the subject experiences a reduction of pain during at least a portion of the application period and for a period of 2 hours to 10 hours after removal of the analgesic system.

22. The method of claim 1, wherein the existing pain is the nerve entrapment pain.

23. The method of claim 22, wherein the nerve entrapment pain is associated with carpal tunnel syndrome, ulnar neuropathy, pudendal nerve entrapment, cubital tunnel syndrome, Guyon canal syndrome, posterior interosseous nerve syndrome, supracapular nerve entrapment, lateral femoral cutaneous nerve entrapment, or Tarsal tunnel syndrome.

24. The method of claim 1, wherein the existing pain is the neuroma pain.

25. The method of claim 1, wherein the neuroma pain is associated with a neoplastic tumor, nerve injury, traumatic neuroma, or Morton'"'"'s neuroma.

26. The method of claim 1, wherein the existing pain is the headache pain.

27. The method of claim 26, wherein the headache pain is associated with occipital neuralgia.

28. The method of claim 1, wherein the existing pain is the connective tissue pain.

29. The method of claim 28, wherein the connective tissue pain is associated with areolar connective tissue, adipose connective tissue, fibrous connective tissue, elastic connective tissue, reticular connective tissue, a tendon, a ligament, an iliotibial band, or a blood vessel.

30. The method of claim 1, wherein the existing pain is the arthritis pain.

31. The method of claim 30, wherein the arthritis pain is osteoarthritis pain or rheumatoid arthritis pain.

32. The method of claim 1, wherein the existing pain is pain associated with injury.

33. The method of claim 32, wherein the injury is a fracture, a severance, a break, a sprain, a strain, a tear, a point pain, a focal pain, or a bruise.

34. The method of claim 1, wherein the existing pain is pain associated with overuse.

35. The method of claim 34, wherein the overuse is related to tendonosis, tendonitis, patellar tendonitis, clavicular tendonitis, medial tibial stress syndrome, focal pain, point pain, or muscle pain.