Pharmaceutical compositions for the nasal delivery of compounds useful for the treatment of osteoporosis

• US 5,977,070 A
• Filed: 08/29/1995
• Issued: 11/02/1999
• Est. Priority Date: 07/14/1992
• Status: Expired due to Fees

• Current Assignee: Syntec Incorporated (Atos SE)
• Original Assignee: Syntec Incorporated (Atos SE)
• Inventors: Vickery, Brian Henry, Krstenansky, John Leonard, Piazza, Christin Teresa, Radomsky, Michael Lloyd, Nestor, John Joseph Jr.
• Primary Examiner(s): Feisee, Lila
• Assistant Examiner(s): LAZAR WESLEY, ELIANE M
• Application Number:
  US08/521,097
• Time in Patent Office: 1,526 Days
• Field of Search: 514/12, 514/2, 514/8, 514/13, 514/14, 514/15, 514/16, 514/17, 514/18, 514/19, 530/324, 530/334, 530/397, 530/399, 435/69.1, 435/69.4, 435/320.1, 435/172.1, 435/6
• US Class Current: 514/11.8
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: C07K 14/635 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

A pharmaceutical composition for the nasal delivery of compounds useful for treating osteoporosis, comprising an effective amount of a physiologically active truncated analog of PTH or PTHrp, or salt thereof, in which amino acid residues (22-31) form an amphipathic α-helix, said residues (22-31) selected from (SEQ ID NOS: 85, 86, 26, 27, 28, 29, and 30); an absorption enhancer selected from the group consisting of dimethyl-β-cyclodextrin and the bile acid surfactants; and water is provided.

Claims

1. A pharmaceutical composition useful for treating osteoporosis, comprising an effective amount of a physiologically active modified PTH or PTHrP, or salt thereof, having bone mass restoring activity in which amino acid residues (22-31) form an amphipathic α

-helix, which differs from naturally occurring PTH or PTHrP by changes comprising substitutions at one or more of positions (22-31), wherein the substitutions are selected from the group consisting of SEQ ID NOS;

85, 86, 26, 27, 28, 29 and 30;

an absorption enhancer selected from the group consisting of dimethyl-β

-cyclodextrin and the bile acid surfactants; and

water.

2. A composition of claim 1 wherein the bile acid surfactant is selected from the salts of glycocholic acid and taurocholic acid.

3. A composition of claim 2 wherein the bile acid surfactant is sodium taurocholate.

4. A composition of claim 2 wherein the bile acid surfactant is sodium glycocholate.

5. A composition of claim 1 wherein the concentration of modified PTH or PTHrP is from 1 mg/ml to about 100 mg/ml.

6. A composition of claim 1 wherein the concentration of absorption enhancer is from about 0.5 to about 50 mg/ml.

7. A composition of claim 1 wherein the modified PTHrP is the compound of SEQ ID NO:

7.

8. A composition of claim 7 wherein the absorption enhancer is dimethyl-β

-cyclodextrin.

9. A composition of claim 7 wherein the absorption enhancer is sodium taurocholate.

10. A composition of claim 7 wherein the absorption enhancer is sodium glycocholate.

11. A pharmaceutical composition comprising from about 1 to about 100 mg/ml of a compound of SEQ ID NO:

7;

from about 0.5 to about 50 mg/ml of an absorption enhancer selected from the group consisting of dimethyl-β

-cyclo-dextrin, sodium glycocholate, and sodium taurocholate; and

water.

12. A method for the intranasal delivery of an PTH or PTHrP analog having bone mass restoring activity which differs from naturally occurring PTH or PTHrP by changes comprising the substitutions at one or more of positions (22-31) wherein the substitutions are selected from the group consisting of SEQ ID NOS:

85, 86, 26, 27, 28, 29, and 30, which method comprises preparing a mixture of;

a) said PTH or PTHrP analog;

b) an absorption enhancer; and

c) water

and administering said mixture to the nasal cavity of a patient in need thereof.

13. A method of claim 12 wherein the absorption enhancer is selected from the group consisting of dimethyl-β

-cyclodextrin and the bile acid surfactants.