Methods and devices for the sustained release of multiple drugs

• US 7,833,545 B2
• Filed: 04/29/2004
• Issued: 11/16/2010
• Est. Priority Date: 04/29/2003
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Langer, Robert S., Ron, Eyal S., Crowley, William F. Jr.
• Primary Examiner(s): Wax; Robert A
• Assistant Examiner(s): Palenik; Jeffrey T
• Application Number:
  US10/835,414
• Publication Number:
  US 20070196433A1
• Time in Patent Office: 2,392 Days
• Field of Search: None
• US Class Current: 424/432
• CPC Class Codes: A61F 6/08 Pessaries, i.e. devices worn in the vagina to support the uterus, remedy a malposition or prevent conception , e.g. combined with devices protecting against contagion
• CPC Class Codes: A61F 6/142 Wirelike structures, e.g. loops, rings, spirals
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

The invention relates to an drug delivery device and a method for delivering multiple drugs over a prolonged period of time. The drug delivery device has two or more unitary segments comprising a drug-permeable polymeric substance, wherein at least one of the segments further comprises a pharmaceutically active agent. The invention also relates to a method for the treatment of a benign ovarian secretory disorder in a female mammal, a method of contraception, and a method of relieving the symptoms associated with menopausal, perimenopausal and post-menopausal periods in a woman.

Claims

1. A drug delivery device, comprising:

a stand-alone implantable body having a homogenous cross-section at all points along the implantable body, the implantable body further having two or more segments, each segment having first and second terminal ends that are each coupled to a terminal end of another segment, each segment having no membrane and having a drug-permeable polymeric substance comprising ethylene-vinyl acetate copolymer, and wherein at least one segment comprises a homogenous mixture of the drug-permeable polymeric substance and a drug such that the at least one segment is configured to release the drug at a substantially zero-order rate.

2. The drug delivery device of claim 1, wherein two or more segments each contain a drug.

3. The drug delivery device of claim 1, wherein the device is suitable for use as a vaginal ring.

4. The drug delivery device of claim 1, wherein the ends of the segments are attached by a coupling means.

5. The drug delivery device of claim 4, wherein the coupling means is an adhesive material.

6. The drug delivery device of claim 3, the vaginal ring having an overall diameter in a range of about 40 mm to 80 mm.

7. The drug delivery device of claim 3, at least one segment having a cross-sectional diameter in a range of about 0.5 mm to 12 mm.

8. The drug delivery device of claim 1, wherein the drug is a hormone replacement steroid.

9. The drug delivery device of claim 1, wherein the drug is a contraceptive agent.

10. The drug delivery device of claim 1, wherein the drug is selected from the group consisting of:

interferon, anti-angiogenesis factors, growth factors, hormones, enzymes, transferases, hydrolases, lysases, isomerases, proteases, ligases and oxidoreductases, enzyme inhibitors, steroids, anti-cancer drugs and antibiotics.

11. The drug delivery device of claim 1, wherein the drug is selected from the group consisting of:

growth hormone, polysaccharides, antigens, and antibodies.

12. A drug delivery device, comprising:

a stand-alone substantially ring-shaped implantable body having a plurality of segments, each segment having a drug-permeable polymeric substance comprising an ethylene-vinyl acetate copolymer; and

at least one segment of the plurality being a homogenous mixture of the drug-permeable polymeric substance and a drug such that the at least one segment is configured to release the drug at a substantially zero-order rate, the at least one segment having a cross-sectional diameter substantially identical to a cross-sectional diameter of the implantable body and having no membrane.

14. The drug delivery device of claim 12, wherein the substantially ring-shaped implantable body is ovular.

15. The drug delivery device of claim 12, wherein the substantially ring-shaped implantable body is circular.

13. A drug delivery device, comprising:

a closed-loop implantable body consisting essentially of two or more segments with at least one end of at least one segment being attached to at least one end of another segment, each segment having no membrane and having a drug-permeable polymeric substance comprising an ethylene-vinyl acetate copolymer, and wherein at least one segment comprises a homogenous mixture of the drug-permeable polymeric substance and a drug such that the at least one segment is configured to release the drug at a substantially zero-order rate.

16. The drug delivery device of claim 13, wherein the closed-loop implantable body is ovular.

17. The drug delivery device of claim 13, wherein the closed-loop implantable body is circular.