Sustained release of peptides from pharmaceutical compositions

• US 5,595,760 A
• Filed: 03/08/1995
• Issued: 01/21/1997
• Est. Priority Date: 09/02/1994
• Status: Expired due to Term

• Current Assignee: Ipsen Pharma Sas (Ipsen Sa)
• Original Assignee: Delab Co.
• Inventors: Cherif-Cheikh, Roland
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Shelborne, Kathryne E.
• Application Number:
  US08/400,610
• Time in Patent Office: 685 Days
• Field of Search: 424/464, 424/422, 424/423, 424/484, 424/488
• US Class Current: 424/464
• CPC Class Codes: A61J 1/201 having one piercing end
• CPC Class Codes: A61J 1/2013 having two piercing ends
• CPC Class Codes: A61J 1/2086 for fluid filtration
• CPC Class Codes: A61J 1/2089 Containers or vials which are to be joined to each other in order to mix their contents combinations of vial and syringe for mixing their contents A61J1/2096
• CPC Class Codes: A61J 1/2096 Combination of a vial and a syringe for transferring or mixing their contents
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 38/25 Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 38/31 Somatostatins
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/1629 Organic macromolecular compounds
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027
• CPC Class Codes: A61M 5/14244 : adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/14248 : of the skin patch type
• CPC Class Codes: A61M 5/2448 : comprising means for injection of two or more media, e.g. by mixing
• CPC Class Codes: A61M 5/284 : comprising means for injection of two or more media, e.g. by mixing
• CPC Class Codes: A61M 5/31505 : Integral with the syringe barrel, i.e. connected to the barrel so as to make up a single complete piece or unit
• CPC Class Codes: A61M 5/31531 : Microsyringes, e.g. having piston bore diameter close or equal to needle shaft diameter

Abstract

The invention features a method of administering a peptide to a patient and delivering the peptide continuously over an extended period of time of at least three days by obtaining a solid pharmaceutical composition including a soluble, gelable salt of the peptide and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, and parenterally administering the solid composition to the patient in one injection, wherein the solid composition automatically forms a gel after interaction with the patient'"'"'s bodily fluids and releases the peptide continuously within the patient over an extended period of at least three days.

Claims

1. A method of administering a peptide to a patient and delivering the peptide continuously over an extended period of time of at least three days, said method comprising

obtaining a solid pharmaceutical composition consisting essentially of a soluble, gelable peptide salt of said peptide and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, wherein said peptide salt and carrier are soluble in aqueous liquids, and

parenterally administering said solid composition to the patient in one injection, wherein said solid composition automatically forms a gel after interaction with the patient'"'"'s bodily fluids, said gel releasing said peptide continuously within the patient over an extended period of at least three days.

2. A method of claim 1, wherein said solid composition is administered intramuscularly, subcutaneously, or intradermally.

3. A method of claim 1, wherein said peptide is somatostatin or a somatostatin analog.

4. A method of claim 1, wherein said peptide is a soluble luteinizing hormone-releasing hormone (LHRH) analog.

5. A method of claim 1, wherein said peptide is growth hormone releasing factor (GRF), parathyroid hormone (PTH), parathyroid hormone related protein (PTHrp), calcitonin, or a soluble, biologically active analog of GRF, PTH, PTHrp, or calcitonin.

6. A method of claim 1, wherein said solid composition comprises no carrier.

7. A method of claim 1, wherein the carrier is selected from the group consisting of mannitol, sorbitol, or lactose.

8. A method of claim 1, wherein said solid composition is in the form of a cylinder with a diameter of less than 3 mm.

9. A method of claim 1, wherein said gel releases said peptide continuously over a period of at least 14 days.

10. A method of administering a peptide to a patient continuously over an extended period of time of at least three days, said method comprising

obtaining a semisolid suspension consisting essentially of (1) a solid, soluble, gelable peptide salt of said peptide, and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, wherein said peptide salt and carrier are soluble in aqueous solvents;

and (2) an aqueous solvent in an amount less than 50 percent of the amount of solvent required to dissolve said peptide salt and to provide said semisolid consistency; and

parenterally administering said semisolid suspension to the patient in one injection, wherein said semisolid suspension automatically forms a gel after interaction with the patient'"'"'s bodily fluids, said gel releasing said peptide continuously within the patient over an extended period of at least three days.

11. A method of claim 10, wherein said peptide is somatostatin or a somatostatin analog.

12. A method of claim 10, wherein said peptide is a soluble luteinizing hormone-releasing hormone (LHRH) analog.

13. A method of claim 10, wherein said peptide is growth hormone releasing factor (GRF), parathyroid hormone (PTH), parathyroid hormone related protein (PTHrp), calcitonin, or a soluble, biologically active analog of GRF, PTH, PTHrp, or calcitonin.

14. A method of claim 10, wherein said amount of solvent is less than 10 percent of the amount of solvent required to dissolve said peptide salt.

15. A sustained-release gel formed within a patient, said gel comprising

a pharmaceutical composition consisting essentially of a soluble, gelable peptide salt and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, wherein said peptide salt and carrier are soluble in aqueous liquids, and

one or more bodily fluids of the patient, wherein said peptide salt automatically forms said gel after interaction with said bodily fluids, and said gel releases said peptide continuously within the patient over a period of at least three days after formation.

16. A gel of claim 15, wherein said pharmaceutical composition is a solid.

17. A gel of claim 15, wherein said pharmaceutical composition further comprises a solvent in an amount less than 50 percent of the amount of solvent required to dissolve said peptide salt and to provide said pharmaceutical composition with a semisolid consistency.

18. A solid, non-particulate, sustained-release pharmaceutical composition for parenteral administration to a patient, said composition consisting essentially of (1) a soluble, gelable peptide salt, and (2) up to 30 percent, by weight, of a pharmaceutically acceptable, monomeric, soluble carrier, compounded into a solid cylindrical form, wherein said peptide salt and carrier are soluble in aqueous liquids and said solid composition automatically forms a gel after interaction with the patient'"'"'s bodily fluids, said gel releasing said peptide continuously within the patient over an extended period of at least three days.

19. A composition of claim 18, wherein said peptide is selected from the group consisting of somatostatin or a somatostatin analog;

a soluble, hydrophobic luteinizing hormone releasing hormone (LHRH) analog;

growth hormone releasing factor (GRF);

parathyroid hormone (PTH);

parathyroid hormone related protein (PTHrp);

calcitonin;

or a soluble, biologically active analog of GRF, PTH, PTHrp, or calcitonin.

20. A semisolid, sustained-release pharmaceutical suspension for parenteral administration to a patient, said suspension consisting essentially of

(1) a soluble, gelable peptide salt and up to 30 percent, by weight, of a pharmaceutically acceptable, soluble, monomeric carrier, wherein said peptide salt and said carrier are soluble in aqueous solvents;

and

(2) an aqueous solvent in an amount less than 50 percent of the amount of solvent required to dissolve said peptide salt and to provide said semisolid consistency of said suspension, wherein said semisolid suspension automatically forms a gel after interaction with the patient'"'"'s bodily fluids, said gel releasing said peptide continuously within the patient over an extended period of at least three days.

21. A suspension of claim 20, wherein said amount of solvent is less than 10 percent of the amount of solvent required to dissolve said peptide salt.

22. A suspension of claim 20, wherein said peptide is selected from the group consisting of somatostatin or a somatostatin analog;

a soluble, hydrophobic luteinizing hormone releasing hormone (LHRH) analog;

growth hormone releasing factor (GRF);

parathyroid hormone (PTH);

parathyroid hormone related protein (PTHrp);

calcitonin;

or a soluble, biologically active analog of GRF, PTH, PTHrp, or calcitonin.