Delivery of dry formulations of octreotide

• US 7,759,312 B2
• Filed: 07/11/2008
• Issued: 07/20/2010
• Est. Priority Date: 03/11/2005
• Status: Active Grant

• Current Assignee: Endo Pharmaceuticals Solutions Incorporated (Endo International PLC)
• Original Assignee: Endo Pharmaceuticals Solutions Incorporated (Endo International PLC)
• Inventors: Kuzma, Petr, Decker, Stefanie
• Primary Examiner(s): Bradley; Christina
• Application Number:
  US12/171,999
• Publication Number:
  US 20090035343A1
• Time in Patent Office: 739 Days
• Field of Search: None
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/31 Somatostatins
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 5/08 for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

Methods and devices are described for delivering octreotide to a patient, comprising implanting a controlled release composition for delivering octreotide, wherein the composition does not require hydration prior to implantation, and wherein the composition optionally comprises a release agent.

Claims

1. A method of delivering octreotide to a subject with a substantially zero-order release profile over an extended period of time, but no less than about six months, the method comprising subcutaneously implanting in the subject at least one implantable device, wherein the at least one implantable device comprises a composition comprising octreotide and hydroxpropylcellulose, wherein the composition is encased in a hydrophilic polymer comprising a co-polymer obtained from the co-polymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers, and wherein the implantable device is implanted in a dry state, such that the subject receives on a daily basis over a period of at least about six months dose amounts of octreotide, which are effective to treat the subject.

2. The method of claim 1, wherein at least one of the two hydrophilic, ethylenically unsaturated monomers is a methacrylate-based monomer.

3. The method of claim 1, wherein the octreotide is in free form, salt form or in the form of a complex thereof.

4. The method of claim 1, wherein the octreotide is octreotide acetate.

5. The method of claim 1, wherein the subject is afflicted with a GH or IGF-1 hormone disorder or its symptoms.

6. The method of claim 5, wherein the GH or IGF-1 disorder is acromegaly.

7. The method of claim 1, wherein the subject receives octreotide at an average rate ranging from about 75 μ

g per day to about 300 μ

g per day over a period of at least about six months.

8. The method of claim 1, wherein the dose amounts of octreotide received by the subject result in octreotide serum levels ranging from about 0.5 ng/ml to about 2 ng/ml.

9. The method of claim 1, wherein the subject receives an effective amount of octreotide for a period of at least about twelve months.

10. The method of claim 1, wherein the dose amounts of octreotide received by the subject result in octreotide serum levels ranging from about 0.8 ng/ml to about 1.8 ng/ml.

11. The method of claim 1, wherein the dose amounts of octreotide received by the subject result in C_max for octreotide serum levels below about 1.3 ng/ml.

12. The method of claim 1, wherein the dose amounts of octreotide received by the subject result in C_max for octreotide serum levels below about 1.0 ng/ml.

13. The method of claim 1, wherein release of octreotide occurs at least three to about ten days after implantation.

14. The method of claim 1, wherein the subject is afflicted with a condition selected from the group consisting of:

carcinoid syndrome, VIPomas, neuroendocrine tumors, proliferative diabetic retinopathy, rosacea, pancreatitis, gastrointestinal bleeding, pancreatic and intestinal fistulas, Graves-Basedow opthalmopathy, glaucoma, and symptoms associated with chemotherapy or AIDS.

15. The method of claim 1, wherein said hydrophilic, ethylenically unsaturated monomers are selected from 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate monomers.

16. The method of claim 1, wherein said copolymer comprises about 20% of 2-hydroxyethyl methacrylate and about 80% hydroxypropyl methacrylate.

17. A method of delivering octreotide to a subject with a substantially zero-order release profile over an extended period of time, but no less than about six months, the method comprising subcutaneously implanting in the subject at least one implantable device, wherein the at least one implantable device comprises a composition comprising hydroxpropylcellulose and from about 20 to about 150 mg of octreotide, in free form or salt form, wherein the composition is encased in a hydrophilic polymer comprising a co-polymer obtained from the co-polymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers, and wherein the implantable device is implanted in a dry state, such that the subject receives on a daily basis over a period of at least about six months dose amounts of octreotide, which are effective to treat the subject.