1. A biodegradable controlled release drug delivery system comprising drug uniformly distributed in poly-4-hydroxybutyrate wherein the drug is incorporated into the polymer at a percent loading of up to 50% by weight of the device.
2. The drug delivery system of claim 1 wherein less than 60% of the drug is released in vitro after 10 days.
3. The drug delivery system of claim 1 wherein less than 35% of the drug is released in vitro after 10 days.
4. The drug delivery system of claim 1 wherein the drug is selected from the group consisting of proteins, peptides, polysaccharides, nucleic acid molecules, and synthetic or natural organic compounds.
5. The drug delivery system of claim 4 wherein the drug is an antibiotic.
6. The drug delivery system of claim 1 wherein the drug is coated onto a medical device.
7. The drug delivery system of claim 1 wherein the device is formed of the poly-4-hydroxybutyrate or copolymer thereof.
8. The drug delivery system of claim 1 wherein the poly-4-hydroxybutyrate or a copolymer thereof is formed of or coated onto a stent.
9. The drug delivery system of claim 1 in a form selected from the group consisting of granules, sheets, films, particles, and molded forms.
10. The drug delivery system of claim 1 wherein the copolymer is a copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate.
11. The drug delivery system of claim 1 wherein the copolymer is a copolymer of 4-hydroxybutyrate and glycolate.
12. The drug delivery system of claim 1 wherein the device exhibits linear release of the drug.
13. The drug delivery system of claim 1 wherein the device exhibits zero-order release of the drug.
14. The drug delivery system of claim 1 wherein the device does not release a burst of drug.
15. The drug delivery system of claim 1 wherein the device releases drug for at least 21 days
16. The drug delivery system of claim 1 wherein the device releases drug for at least one month.
17. The drug delivery system of claim 1 wherein the device releases drug for at least three months.
18. The drug delivery system of claim 1 wherein the device releases drug for at least six months.
19. A method of delivering a drug comprising administering to an individual in need thereof a biodegradable controlled release drug delivery system comprising drug uniformly distributed in poly-4-hydroxybutyrate wherein the drug is incorporated into the polymer at a percent loading of up to 50% by weight of the device.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of manufacturing a ferrule, the method comprising:
cold forming a transition sleeve, the transition sleeve having an inner surface and an outer surface, a first end that is attachable to a stem, a second end that has an annular indented seat in the inner surface or the outer surface thereof, and a bell-shaped body extending from the first end to the second end;
providing a penetration sleeve comprising a plurality of inwardly directed and axially spaced apart attachment means for penetrating into a hose when said ferrule is radially inwardly deformed; and
brazing the penetration sleeve to the annular indented seat in the transition sleeve to form a one-piece assembly.
2. The method of claim 1 wherein the penetration sleeve is a non-machined piece.
3. The method of claim 1 further comprising machining the penetration sleeve from tubing.
4. The method of claim 1 further comprising roll forming the penetration sleeve.
5. The method of claim 1 wherein the attachment means include barbs capable of penetrating a hose.
6. The method of claim 1 wherein the attachment means include axially spaced apart ribs.
7. The method of claim 1 wherein the annular indented seat is in the inner surface of the transition sleeve and is long enough to encapsulate the penetration sleeve.
8. The method of claim 7 wherein the penetration sleeve comprises two or more pieces brazed to the annular indented seat.
9. The method of claim 1 wherein the ferrule can withstand hydrostatic pressures greater than four times the working pressures of the hose.
10. The method of claim 1 wherein the annular indented seat is on the outer surface of the second end of the transition sleeve.
11. A ferrule prepared by the method of claim 1.
12. A method of manufacturing a ferrule, the method comprising:
forming a transition sleeve without machining, the transition sleeve having an inner surface and an outer surface, a first end that is attachable to a stem, a second end that has an annular indented seat in the inner surface or the outer surface thereof, and a bell-shaped body extending from the first end to the second end; and
brazing a penetration sleeve comprising a plurality of inwardly directed and axially spaced apart attachment means for penetrating into a hose when said ferrule is radially inwardly deformed to the annular indented seat in the transition sleeve.
13. The method of claim 12 wherein forming includes cold forming, sintering, or die casting the transition sleeve.
14. The method of claim 12 wherein brazing includes copper brazing.
15. The method of claim 12 further comprising:
providing a stem; and
brazing the first end of the transition sleeve to the stem to form a coupling.
16. The method of claim 15 wherein brazing includes copper brazing.
17. The method of claim 12 wherein the annular indented seat is on the outer surface of the second end of the transition sleeve.
18. A ferrule prepared by the method of claim 12.
19. A method of manufacturing a ferrule, the method comprising:
cold forming a transition sleeve, the transition sleeve having an inner surface and an outer surface, a first end that is attachable to a stem, a second end that has an annular indented seat in the inner surface, and a bell-shaped body extending from the first end to the second end;
providing a sintered penetration sleeve comprising a plurality of inwardly directed and axially spaced apart attachment means for penetrating into a hose when said ferrule is radially inwardly deformed; and
sintering the penetration sleeve to the annular indented seat in the transition sleeve to form a single-piece ferrule.
20. The method of claim 19 wherein the penetration sleeve is a non-machined piece.