Mast cell stabilizers treatment for systemic disorders

• US 10,238,628 B2
• Filed: 04/19/2018
• Issued: 03/26/2019
• Est. Priority Date: 02/10/2014
• Status: Expired due to Fees

• Current Assignee: Respivant Sciences GmbH
• Original Assignee: Respivant Sciences GmbH
• Inventors: Gerhart, William, Keller, Manfred, Tutuncu, Ahmet, Soni, Pravin
• Primary Examiner(s): Rao, Savitha M
• Application Number:
  US15/957,719
• Publication Number:
  US 20180271828A1
• Time in Patent Office: 341 Days
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: H05K 999/99 dummy group
• 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

Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders, are provided.

Claims

1. A method of treating an inflammatory disorder in a patient, comprising administering to the patient a pharmaceutical composition comprising cromolyn sodium using a device that produces an aerosol of the pharmaceutical composition exhibiting a respirable fraction (≤

5 μ

m) of at least about 60%, and wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC<sub>(0-∞

)</sub> of cromolyn greater than about 5.3 ng*h/mL per milligram of cromolyn sodium administered to the patient.

2. The method of claim 1, wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC_(0-∞

) of cromolyn greater than about 6.6 ng*h/mL per milligram of cromolyn sodium administered to the patient.

3. The method of claim 1, wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC_(0-∞

) of cromolyn greater than about 8.5 ng*h/mL per milligram of cromolyn sodium administered to the patient.

4. The method of claim 1, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

5. The method of claim 1, wherein the administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 2.2 ng/mL per milligram of cromolyn sodium administered to the patient.

6. The method of claim 5, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

27. The method of claim 4, wherein the device is a nebulizer or a high-efficiency nebulizer.

28. The method of claim 27, wherein the device is a high-efficiency nebulizer.

31. The method of claim 1, wherein the aerosol of the pharmaceutical composition further exhibits a respirable fraction (≤

3.3 μ

m) of at least about 30%.

32. The method of claim 31, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

33. The method of claim 32, wherein the device is a high-efficiency nebulizer.

7. A method of treating an inflammatory disorder in a patient, comprising administering to the patient a pharmaceutical composition comprising cromolyn sodium using a device that produces an aerosol of the pharmaceutical composition exhibiting a respirable fraction (≤

5 μ

m) of at least about 60%, and wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 2.2 ng/mL per milligram of cromolyn sodium administered to the patient.

8. The method of claim 7, wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 3 ng/mL per milligram of cromolyn sodium administered to the patient.

9. The method of claim 7, wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 3.9 ng/mL per milligram of cromolyn sodium administered to the patient.

10. The method of claim 7, wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC_(0-∞

) of cromolyn greater than about 6.6 ng*h/mL per milligram of cromolyn sodium administered to the patient.

11. The method of claim 7, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

34. The method of claim 7, wherein the aerosol of the pharmaceutical composition further exhibits a respirable fraction (≤

3.3 μ

m) of at least about 30%.

35. The method of claim 34, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

36. The method of claim 35, wherein the device is a high-efficiency nebulizer.

12. A method of treating fibrosis in a patient, comprising administering to the patient a pharmaceutical composition comprising cromolyn sodium using a device that produces an aerosol of the pharmaceutical composition exhibiting a respirable fraction (≤

5 μ

m) of at least about 60%, and wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC<sub>(0-∞

)</sub> of cromolyn greater than about 5.3 ng*h/mL per milligram of cromolyn sodium administered to the patient.

13. The method of claim 12, wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC_(0-∞

) of cromolyn greater than about 6.6 ng*h/mL per milligram of cromolyn sodium administered to the patient.

14. The method of claim 12, wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC_(0-∞

) of cromolyn greater than about 8.5 ng*h/mL per milligram of cromolyn sodium administered to the patient.

15. The method of claim 12, wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 2.2 ng/mL per milligram of cromolyn sodium administered to the patient.

16. The method of claim 12, wherein said fibrosis is kidney fibrosis.

17. The method of claim 12, wherein said fibrosis is hepatic fibrosis.

18. The method of claim 12, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

19. The method of claim 12, wherein the administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 3 ng/mL per milligram of cromolyn sodium administered to the patient.

29. The method of claim 18, wherein the device is a nebulizer or a high-efficiency nebulizer.

30. The method of claim 29, wherein the device is a high-efficiency nebulizer.

37. The method of claim 12, wherein the aerosol of the pharmaceutical composition further exhibits a respirable fraction (≤

3.3 μ

m) of at least about 30%.

38. The method of claim 37, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

39. The method of claim 38, wherein the device is a high-efficiency nebulizer.

20. A method of treating fibrosis in a patient, comprising administering to the patient a pharmaceutical composition comprising cromolyn sodium using a device that produces an aerosol of the pharmaceutical composition exhibiting a respirable fraction (≤

5 μ

m) of at least about 60%, and wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 2.2 ng/mL per milligram of cromolyn sodium administered to the patient.

21. The method of claim 20, wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 3 ng/mL per milligram of cromolyn sodium administered to the patient.

22. The method of claim 20, wherein administration of the pharmaceutical composition to the patient produces in the patient a C_max of cromolyn greater than about 3.9 ng/mL per milligram of cromolyn sodium administered to the patient.

23. The method of claim 20, wherein administration of the pharmaceutical composition to the patient produces in the patient an AUC_(0-∞

) of cromolyn greater than about 6.6 ng*h/mL per milligram of cromolyn sodium administered to the patient.

24. The method of claim 20, wherein said fibrosis is kidney fibrosis.

25. The method of claim 20, wherein said fibrosis is hepatic fibrosis.

26. The method of claim 20, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

40. The method of claim 20, wherein the aerosol of the pharmaceutical composition further exhibits a respirable fraction (≤

3.3 μ

m) of at least about 30%.

41. The method of claim 40, wherein the device is a nebulizer, a high-efficiency nebulizer, or a dry powder inhaler.

42. The method of claim 41, wherein the device is a high-efficiency nebulizer.