IP Library Granted Patent US 8,138,149
Granted Patent B2
US 8,138,149 · App. 12/878,936 · Granted Mar 20, 2012

Nasal calcitonin formulations containing chlorobutanol

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Quick Facts
Patent No.
US 8,138,149
App. No.
12/878,936
Granted
Mar 20, 2012
Kind
B2
Abstract

An aqueous solution of calcitonin suitable for intranasal administration comprised of calcitonin, chlorobutanol at a concentration of less than 0.4% weight/weight, and water and having a pH of less than 4 with the proviso that benzalkonium chloride is not present in the solution. The aqueous solution of calcitonin can be used to treat osteoporosis, Paget's bone disease and hypercalcemia.

Claims (17)

1. A method for intranasal administration of calcitonin which comprises administering intranasally to an individual a solution of calcitonin comprising calcitonin, water, sodium chloride and only one preservative, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight.

2. The method of claim 1 , wherein the calcitonin is present in the solution at a concentration of about 0.0355 weight/weight, the sodium chloride is present in the solution at a concentration of about 0.85%, and the solution has a pH of less than 4 and an oxygen at a content of less than about 5%.

3. The method of claim 1 , wherein the solution of calcitonin is administered into a nose of an individual through an actuator tip as a spray, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.

4. The method of claim 3 , wherein the spray produces droplets, wherein less that 5% of the droplets are less than 10 microns in size.

5. The method of claim 3 , wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.

6. A composition comprising calcitonin, water, sodium chloride and only one preservative, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight, and wherein the composition is suitable for intranasal administration in humans.

7. A composition consisting essentially of calcitonin, water, sodium chloride, a single preservative and optionally hydrochloric acid, wherein the single preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight, and wherein the composition is suitable for intranasal administration in humans.

8. A composition consisting essentially of a solution of (i) calcitonin, (ii) chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight, (iii) water, (iv) sodium chloride, and optionally (v) hydrochloric acid, wherein the composition has a pH of 4 or less, and wherein the composition is suitable for intranasal administration in humans.

9. A pharmaceutical device comprising a composition according to claim 6 and an actuator to produce an aerosol spray of the composition, the spray having a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.

10. A pharmaceutical device comprising a composition according to claim 6 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.

11. A pharmaceutical device comprising a composition according to claim 6 and an actuator to produce an aerosol spray of the composition, the spray having a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip, wherein less than 5% of the droplets are smaller than 10 microns in size.

12. A pharmaceutical device comprising a composition according to claim 7 and an actuator to produce an aerosol spray of the composition, the spray having a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.

13. A pharmaceutical device comprising a composition according to claim 7 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.

14. A pharmaceutical device comprising a composition according to claim 7 and an actuator to produce an aerosol spray of the composition, the spray having a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip, wherein less than 5% of the droplets are smaller than 10 microns in size.

15. A pharmaceutical device comprising a composition according to claim 8 and an actuator to produce an aerosol spray of the composition, the spray having a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.

16. A pharmaceutical device comprising a composition according to claim 8 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.

17. A pharmaceutical device comprising a composition according to claim 8 and an actuator to produce an aerosol spray of the composition, the spray having a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip, wherein less than 5% of the droplets are smaller than 10 microns in size.

Assignments (15)
SECURITY INTEREST Recorded Jul 22, 2024
From: ENDO BIOLOGICS LIMITED; ENDO OPERATIONS LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 068469/0001 →
SECURITY INTEREST Recorded Jul 19, 2024
From: ENDO BIOLOGICS LIMITED; ENDO OPERATIONS LIMITED
To: GOLDMAN SACHS BANK USA
Reel/Frame 068461/0692 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2024
From: ENDO USA, INC.
To: ENDO OPERATIONS LIMITED
Reel/Frame 067245/0492 →
RELEASE OF SECURITY INTEREST Recorded Apr 26, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH HOLDINGS, LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO GENERIC HOLDINGS, INC. (FORMERLY KNOWN AS PAR PHARMACEUTICALS COMPANIES, INC.); ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067240/0001 →
RELEASE OF SECURITY INTEREST Recorded Apr 25, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR PHARMACEUTICAL COMPANIES, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067239/0491 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 23, 2024
From: PAR PHARMACEUTICAL, INC.
To: ENDO USA, INC.
Reel/Frame 067203/0686 →
CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Sep 17, 2021
From: ASTORA WOMEN'S HEALTH LLC; ENDO PHARMACEUTICALS SOLUTIONS INC.; ENDO PHARMACEUTICALS INC.; PAR PHARMACEUTICAL, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 057538/0978 →
SECURITY INTEREST Recorded Jun 8, 2017
From: PAR PHARMACEUTICAL, INC
To: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS COLLATERAL TRUSTEE
Reel/Frame 042743/0216 →
RELEASE OF SECURITY INTEREST Recorded Apr 28, 2017
From: DEUTSCHE BANK AG NEW YORK BRANCH
To: PAR PHARMACEUTICAL, INC.; ENDO GENERICS HOLDINGS, INC.; INNOTEQ, INC.
Reel/Frame 042171/0036 →
RELEASE OF SECURITY INTEREST Recorded Sep 30, 2015
From: BANK OF AMERICA, N.A.
To: PAR PHARMACEUTICAL, INC.; INNOTEQ, INC.; PAR PHARMACEUTICAL COMPANIES, INC.
Reel/Frame 036695/0782 →
CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Sep 25, 2015
From: PAR PHARMACEUTICAL, INC.
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 036687/0821 →
SECURITY AGREEMENT Recorded Oct 1, 2012
From: PAR PHARMACEUTICAL COMPANIES, INC.; PAR PHARMACEUTICAL, INC.
To: BANK OF AMERICA, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 029061/0252 →
CHANGE OF NAME Recorded Aug 29, 2012
From: NASTECH PHARMACEUTICAL COMPANY, INC.
To: MDRNA, INC.
Reel/Frame 028884/0571 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2012
From: MDRNA, INC.
To: PAR PHARMACEUTICAL, INC.
Reel/Frame 028872/0280 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2012
From: QUAY, STEVEN C.; DE MEIRELES, JORGE C.; DESHPANDE, ARATI A.; GO, ZENAIDA O.; SILENO, ANTHONY P.
To: NASTECH PHARMACEUTICAL COMPANY, INC.
Reel/Frame 028872/0173 →