Ring-shaped devices

Abstract

The invention relates to a ring-shaped device comprising: (a) a first compartment comprising an non-medicated core of ethylenes˜vinylacetate copolymer, encircled by a steroid hormone loaded ethylene-vinylacetate copolymer layer, and a non-medicated outer layer of ethylene-vinylacetate copolymer; (b) a second compartment comprising a core of ethylene-vinylacetate copolymer loaded with a steroid hormone and a non-medicated outer layer of ethylene-vinylacetate polymer; and (c) optionally placebo segments of a thermoplastic material separating the first from the second compartment. Preferably, the invention is a two-compartment vaginal ring, the first compartment comprising crystalline etonogestrel and the second compartment comprising a (sub)-saturated mixture of etonogestrel and ethinyl estradiol, both compartments optionally being separated from each other by placebo segments of high density polyethylene.

What is claimed is:  
     
         1 . A ring-shaped device, comprising: 
 a first compartment comprising a non-medicated core of ethylene-vinylacetate copolymer, encircled by a crystalline, steroid hormone saturated ethylene-vinylacetate copolymer middle layer, and a non-medicated outer layer of ethylene-vinylacetate copolymer; and    a second compartment comprising a core of ethylene-vinylacetate copolymer loaded with a steroid hormone and a non-medicated outer layer of ethylene-vinylacetate copolymer;    wherein an initial release of the crystalline, steroid hormone from the first compartment and the steroid hormone from the second compartment lacks a burst effect.    
     
     
         2 . The ring-shaped device of clam  1 , wherein the crystalline, steroid hormone of the middle layer of the first compartment is a progestogen, and the steroid hormone of the ethylene-vinylacetate copolymer core of the second compartment is a mixture of a progestogen and an estrogen.  
     
     
         3 . The ring-shaped device of  claim 2 , wherein the ethylene-vinylacetate copolymer core of the second compartment is loaded with a sub-saturated mixture of the progestogen and the estrogen.  
     
     
         4 . The ring-shaped device of  claim 1 , wherein the first and second compartment lengths have a ratio of between 15:1 and 1:1.  
     
     
         5 . The ring-shaped device of  claim 1 , further comprising at least one placebo segment of a thermoplastic material separating said first compartment from said second compartment.  
     
     
         6 . The ring-shaped device of  claim 5 , wherein a diameter of the ring-shaped device is about 53.5 mm, a cross-sectional diameter of the ring-shaped device is about 3.5 mm, a length of the first compartment is about 100 to 110 mm, a length of the second compartment is about 10 to 40 mm, and a length of the at least one placebo segment is about 5 to 20 mm.  
     
     
         7 . The ring-shaped device of  claim 5 , wherein said thermoplastic material is high density polyethylene.  
     
     
         8 . The ring-shaped device of  claim 5 , wherein a length of the at least one placebo segment is sufficient to prevent substantial mixing of the crystalline, steroid hormone of the first compartment with the steroid hormone of the second compartment.  
     
     
         9 . The ring-shaped device of  claim 8 , wherein the at least one placebo segment is approximately at least half of the length of the second compartment.  
     
     
         10 . The ring-shaped device of  claim 2 , wherein the progestogen is etonogestrel and the estrogen is ethinyl estradiol.  
     
     
         11 . The ring-shaped device of  claim 10 , wherein the middle ethylene-vinylacetate copolymer layer of the first compartment is loaded with about 15% w/w of etonogestrel, and the ethylene-vinylacetate copolymer core of the second compartment is loaded with about 0.25 to 0.5% w/w of etonogestrel and about 0.75 to 1.5% w/w of ethinyl estradiol.  
     
     
         12 . The ring-shaped device of  claim 4 , wherein the ratio is about 2:1.  
     
     
         13 . The ring-shaped device of  claim 1 , wherein the ring diameter is about 53.5 mm, the cross-sectional diameter is about 3.5 mm, the length of the first compartment is about 100 to 110 mm, and the length of the second compartment is about 42 to 52 mm.  
     
     
         14 . The ring-shaped device of  claim 11 , wherein, at least, 90 μg/day of etonogestrel and 10 μg/day of ethinyl estradiol release from the ring-shaped device.  
     
     
         15 . The ring-shaped device of  claim 14 , wherein, at most, 450 μg/day of etonogestrel and 100 μg/day of ethinyl estradiol release from the ring-shaped device during days 1-3.  
     
     
         16 . The ring-shaped device of  claim 15 , wherein, at most, 150 μg/day of etonogestrel and 20 μg/day of ethinyl estradiol release from the ring-shaped device during days 4-21.  
     
     
         17 . A method for manufacturing a ring-shaped device, said method comprising: 
 co-extruding a non-medicated core, a middle layer, and a non-medicated outer layer of ethylene-vinylacetate copolymer into a first fiber;    co-extruding a core and a non-medicated outer layer of ethylene-vinylacetate copolymer into a second fiber; and    melting the first fiber and the second fiber to at least one placebo segment in a mold to form the ring-shaped device.    
     
     
         18 . The method according to  claim 17 , further comprising welding the first compartment to the second compartment.  
     
     
         19 . The method according to  claim 17 , further comprising saturating the middle layer of the first compartment with crystalline, steroid hormone during the co-extrusion.  
     
     
         20 . The method according to  claim 17 , wherein said at least one placebo segment is thermoplastic material.