Methods for the treatment of mast cell related disorders with mast cell stabilizers

• US 10,391,078 B2
• Filed: 02/20/2019
• Issued: 08/27/2019
• Est. Priority Date: 08/07/2015
• Status: Active Grant

• Current Assignee: Respivant Sciences GmbH
• Original Assignee: Respivant Sciences GmbH
• Inventors: Gerhart, William, Soni, Pravin, Tutuncu, Ahmet
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US16/280,829
• Publication Number:
  US 20190183846A1
• Time in Patent Office: 188 Days
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• 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: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

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

Claims

1. A method of treating a subject having a mast cell related disorder, comprising administering to the subject an effective amount of a composition comprising cromolyn, or a salt thereof, using an inhalation device that produces in the subject an AUC_(0-∞

) of cromolyn of from about 5.3 ng*h/mL to about 8.5 ng*h/mL per milligram of cromolyn, or a salt thereof, administered to the subject, and wherein the mast cell related disorder is selected from primary biliary cirrhosis, secondary sclerosing cholangitis due to mast cell cholangiopathy, itching caused by or associated with primary biliary cirrhosis, bronchiolitis obliterans syndrome after lung transplantation, bronchopulmonary dysplasia in infants, cardiac fibrosis, atrial fibrosis, primary sclerosing cholangitis (PSC), chronic pelvic pain syndrome (prostatitis), viral pneumonia caused by respiratory syncytial virus, and interstitial lung disease.

2. The method of claim 1, wherein administration of the composition to the subject produces in the subject a C_max of cromolyn of from about 2.2 ng/mL to about 3.9 ng/mL per milligram of cromolyn, or a salt thereof, administered to the subject.

3. The method of claim 2, wherein the inhalation device is selected from nebulizers, metered dose inhalers, dry powder inhalers, jet nebulizers, ultrasonic wave nebulizers, heat vaporizers, and soft mist inhalers.

4. The method of claim 3, wherein the inhalation device is a nebulizer.

5. The method of claim 4, wherein the nebulizer is a high-efficiency nebulizer.

6. The method of claim 3, wherein the inhalation device is a dry powder inhaler.

7. The method of claim 1, wherein the inhalation device is selected from nebulizers, metered dose inhalers, dry powder inhalers, jet nebulizers, ultrasonic wave nebulizers, heat vaporizers, and soft mist inhalers.

8. The method of claim 7, wherein the inhalation device is a nebulizer.

9. The method of claim 8, wherein the nebulizer is a high-efficiency nebulizer.

10. The method of claim 7, wherein the inhalation device is a dry powder inhaler.

11. The method of claim 1, wherein the mast cell related disorder is selected from primary biliary cirrhosis, secondary sclerosing cholangitis due to mast cell cholangiopathy, itching caused by or associated with primary biliary cirrhosis, primary sclerosing cholangitis (PSC), viral pneumonia caused by respiratory syncytial virus, interstitial lung disease and bronchopulmonary dysplasia in infants.

12. The method of claim 11, wherein the mast cell related disorder is selected from primary sclerosing cholangitis (PSC), viral pneumonia caused by respiratory syncytial virus, interstitial lung disease, and bronchopulmonary dysplasia in infants.

13. The method of claim 12, wherein the mast cell related disorder is primary sclerosing cholangitis (PSC).

14. The method of claim 12, wherein the mast cell related disorder is viral pneumonia caused by respiratory syncytial virus.

15. The method of claim 12, wherein the mast cell related disorder is interstitial lung disease.

16. The method of claim 12, wherein the mast cell related disorder is bronchopulmonary dysplasia in infants.

17. The method of claim 1, wherein the salt of cromolyn is selected from cromolyn sodium, cromolyn lysinate, ammonium cromoglycate, and magnesium cromoglicate.

18. The method of claim 17, wherein the salt of cromolyn is cromolyn sodium.

19. A method of treating a subject having a mast cell related disorder, comprising administering to the subject an effective amount of a composition comprising cromolyn, or a salt thereof, using an inhalation device that produces in the subject a Cmax of cromolyn of from about 2.2 ng/mL to about 3.9 ng/mL per milligram of cromolyn, or a salt thereof, administered to the subject, and wherein the mast cell related disorder is selected from primary biliary cirrhosis, secondary sclerosing cholangitis due to mast cell cholangiopathy, itching caused by or associated with primary biliary cirrhosis, bronchiolitis obliterans syndrome after lung transplantation, bronchopulmonary dysplasia in infants, cardiac fibrosis, atrial fibrosis, primary sclerosing cholangitis (PSC), chronic pelvic pain syndrome (prostatitis), viral pneumonia caused by respiratory syncytial virus, and interstitial lung disease.

20. The method of claim 19, wherein the inhalation device is selected from nebulizers, metered dose inhalers, dry powder inhalers, jet nebulizers, ultrasonic wave nebulizers, heat vaporizers, and soft mist inhalers.

21. The method of claim 20, wherein the inhalation device is a nebulizer.

22. The method of claim 21, wherein the nebulizer is a high-efficiency nebulizer.

23. The method of claim 20, wherein the inhalation device is a dry powder inhaler.

24. The method of claim 19, wherein the mast cell related disorder is selected from primary biliary cirrhosis, secondary sclerosing cholangitis due to mast cell cholangiopathy, itching caused by or associated with primary biliary cirrhosis, primary sclerosing cholangitis (PSC), viral pneumonia caused by respiratory syncytial virus, interstitial lung disease and bronchopulmonary dysplasia in infants.

25. The method of claim 24, wherein the mast cell related disorder is selected from primary sclerosing cholangitis (PSC), viral pneumonia caused by respiratory syncytial virus, interstitial lung disease, and bronchopulmonary dysplasia in infants.

26. The method of claim 25, wherein the mast cell related disorder is primary sclerosing cholangitis (PSC).

27. The method of claim 25, wherein the mast cell related disorder is viral pneumonia caused by respiratory syncytial virus.

28. The method of claim 25, wherein the mast cell related disorder is interstitial lung disease.

29. The method of claim 25, wherein the mast cell related disorder is bronchopulmonary dysplasia in infants.

30. The method of claim 19, wherein the salt of cromolyn is cromolyn sodium.